Medicine › Oncology

Cancer Risks and Factors

Works Count: 36691

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This cluster of papers explores the relationship between obesity, adiposity, and body mass index with cancer risk, prognosis, and treatment outcomes. It covers various aspects such as breast cancer, pregnancy-associated breast cancer, metabolic syndrome, hormonal influences, chemotherapy effects, and survival rates in relation to obesity.

Keywords

Obesity; Cancer; Body Mass Index; Breast Cancer; Pregnancy; Adiposity; Metabolic Syndrome; Chemotherapy; Hormones; Survival

Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies

1996-06-01

BACKGROUND The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed the worldwide epidemiological evidence on the relation between breast cancer risk and use of hormonal … BACKGROUND The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed the worldwide epidemiological evidence on the relation between breast cancer risk and use of hormonal contraceptives. METHODS Individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 studies conducted in 25 countries were collected, checked, and analysed centrally. Estimates of the relative risk for breast cancer were obtained by a modification of the Mantel-Haenszel method. All analyses were stratified by study, age at diagnosis, parity, and, where appropriate, the age a woman was when her first child was born, and the age she was when her risk of conception ceased. FINDINGS The results provide strong evidence for two main conclusions. First, while women are taking combined oral contraceptives and in the 10 years after stopping there is a small increase in the relative risk of having breast cancer diagnosed (relative risk [95 percent CI] in current users 1.24 [1.15-1.33], 2p<0.00001; 1-4 years after stopping 1.16 [1.08-1.23], 2p=0.00001; 5-9 years after stopping 1.07 [1.02-1.13], 2p=0.009). Second, there is no significant excess risk of having breast cancer diagnosed 10 or more years after stopping use (relative risk 1.01 [0.96-1.05], NS). The cancers diagnosed in women who had used combined oral contraceptives were less advanced clinically than those diagnosed in women who had never used these contraceptives for ever-users compared with never-users, the relative risk for tumours that had spread beyond the breast compared with localised tumours was 0.88 (0.81-0.95; 2p=0.002). There was no pronounced variation in the results for recency of use between women with different background risks of breast cancer, including women from different countries and ethnic groups, women with different reproductive histories, and those with or without a family history of breast cancer. The studies included in this collaboration represent about 90 percent of the epidemiological information on the topic, and what is known about the other studies suggests that their omission has not materially affected the main conclusions. Other features of hormonal contraceptive use such as duration of use, age at first use, and the dose and type of hormone within the contraceptives had little additional effect on breast cancer risk, once recency of use had been taken into account. Women who began use before age 20 had higher relative risks of having breast cancer diagnosed while they were using combined oral contraceptives and in the 5 years after stopping than women who began use at older ages, but the higher relative risks apply at ages when breast cancer is rare and, for a given duration of use, earlier use does not result in more cancers being diagnosed than use beginning at older ages. Because breast cancer incidence rises steeply with age, the estimated excess number of cancers diagnosed in the period between starting use and 10 years after stopping increases with age at last use: for example, among 10 000 women from Europe or North America who used oral contraceptives from age 16 to 19, from age 20 to 24, and from age 25 to 29, respectively, the estimated excess number of cancers diagnosed up to 10 years after stopping use is 0.5 (95 percent CI 0.3-0.7), 1.5 (0.7-2.3), and 4.7 (2.7-6.7). Up to 20 years after cessation of use the difference between ever-users and never-users is not so much in the total number of cancers diagnosed, but in their clinical presentation, with the breast cancers diagnosed in ever-users being less advanced clinically than those diagnosed in never-users. The relation observed between breast cancer risk and hormone exposure is unusual, and it is not possible to infer from these data whether it is due to an earlier diagnosis of breast cancer in ever-users, the biological effects of hormonal contraceptives, or a combination of reasons...

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Body Mass Index, Serum Sex Hormones, and Breast Cancer Risk in Postmenopausal Women

2003-08-19

T J Key , P N Appleby , Gillian Reeves +7 more

Background: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum … Background: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. Methods: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case–control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. Results: Breast cancer risk increased with increasing BMI (Ptrend = .002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non–sex hormone–binding globulin–bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone–binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. Conclusion: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.

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Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50 302 women with breast cancer and 96 973 women without the disease

2002-07-01

Henrik Møller , Håkan Olsson , Jonas Ranstam

Estrogens, Progestogens, Normal Breast Cell Proliferation, and Breast Cancer Risk

1993-01-01

Malcolm C. Pike , Darcy Spicer , Laila Dahmoush +1 more

Journal Article Estrogens, Progestogens, Normal Breast Cell Proliferation, and Breast Cancer Risk Get access Malcolm C. Pike, Malcolm C. Pike 1Department of Preventive Medicine, School of Medicine, University of Southern … Journal Article Estrogens, Progestogens, Normal Breast Cell Proliferation, and Breast Cancer Risk Get access Malcolm C. Pike, Malcolm C. Pike 1Department of Preventive Medicine, School of Medicine, University of Southern CaliforniaLos Angeles, CA Dr. Malcolm C. Pike, Department of Preventive Medicine, School of Medicine, University of Southern California, 1420 San Pablo Street, PMB A 201, Los Angeles, CA 90033-9987 Search for other works by this author on: Oxford Academic PubMed Google Scholar Darcy V. Spicer, Darcy V. Spicer 2Department of Medicine, School of Medicine, University of Southern CaliforniaLos Angeles, CA Search for other works by this author on: Oxford Academic PubMed Google Scholar Laila Dahmoush, Laila Dahmoush 3Department of Pathology, School of Medicine, University of Southern CaliforniaLos Angeles, CA Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael F. Press Michael F. Press 3Department of Pathology, School of Medicine, University of Southern CaliforniaLos Angeles, CA Search for other works by this author on: Oxford Academic PubMed Google Scholar Epidemiologic Reviews, Volume 15, Issue 1, 1993, Pages 17–30, https://doi.org/10.1093/oxfordjournals.epirev.a036102 Published: 01 March 1993 Article history Received: 19 January 1993 Published: 01 March 1993 Revision received: 16 April 1993

Etiology of Human Breast Cancer: A Review2

1973-01-01

Brian MacMahon , Philip Cole , James B. Brown

Journal Article Etiology of Human Breast Cancer: A Review Get access Brian MacMahon, M.D., Brian MacMahon, M.D. Department of Epiaemiology, Harvard School of Public Health, Boston, Massachusetts 02115, and Department … Journal Article Etiology of Human Breast Cancer: A Review Get access Brian MacMahon, M.D., Brian MacMahon, M.D. Department of Epiaemiology, Harvard School of Public Health, Boston, Massachusetts 02115, and Department of Obstetrics ana Gynecology, University of Melbourne, Melbourne, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar Philip Cole, M.D., Philip Cole, M.D. Department of Epiaemiology, Harvard School of Public Health, Boston, Massachusetts 02115, and Department of Obstetrics ana Gynecology, University of Melbourne, Melbourne, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar James Brown, Ph.D. James Brown, Ph.D. Department of Epiaemiology, Harvard School of Public Health, Boston, Massachusetts 02115, and Department of Obstetrics ana Gynecology, University of Melbourne, Melbourne, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 1, January 1973, Pages 21–42, https://doi.org/10.1093/jnci/50.1.21 Published: 01 January 1973 Article history Received: 04 August 1972 Accepted: 14 August 1972 Published: 01 January 1973

Overweight as an avoidable cause of cancer in Europe

2001-02-01

Anna Bergström , Paola Pisani , Vanessa Tenet +2 more

There is growing evidence that excess body weight increases the risk of cancer at several sites, including kidney, endometrium, colon, prostate, gallbladder and breast in post-menopausal women. The proportion of … There is growing evidence that excess body weight increases the risk of cancer at several sites, including kidney, endometrium, colon, prostate, gallbladder and breast in post-menopausal women. The proportion of all cancers attributable to overweight has, however, never been systematically estimated. We reviewed the epidemiological literature and quantitatively summarised, by meta-analysis, the relationship between excess weight and the risk of developing cancer at the 6 sites listed above. Estimates were then combined with sex-specific estimates of the prevalence of overweight [body mass index (BMI) 25-29 kg/m(2)] and obesity (BMI > or = 30 kg/m(2)) in each country in the European Union to obtain the proportion of cancers attributable to excess weight. Overall, excess body mass accounts for 5% of all cancers in the European Union, 3% in men and 6% in women, corresponding to 27,000 male and 45,000 female cancer cases yearly. The attributable proportion varied, in men, between 2.1% for Greece and 4.9% for Germany and, in women, between 3.9% for Denmark and 8.8% for Spain. The highest attributable proportions were obtained for cancers of the endometrium (39%), kidney (25% in both sexes) and gallbladder (25% in men and 24% in women). The largest number of attributable cases was for colon cancer (21,500 annual cases), followed by endometrium (14,000 cases) and breast (12,800 cases). Some 36,000 cases could be avoided by halving the prevalence of overweight and obese people in Europe.

Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis

2010-06-22

Melinda M. Protani , Michael Coory , Jennifer Martin

Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms

2004-07-30

Eugenia E. Calle , Rudolf Kaaks

Overweight, obesity, and cancer risk

2002-09-01

Franca Bianchini , Rudolf Kaaks , Harri Vainio

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Dual Effects of Weight and Weight Gain on Breast Cancer Risk

1997-11-05

Zhiping Huang , Susan E. Hankinson , Graham A. Colditz +7 more

Breast cancer is a major cause of mortality among women. It is important to identify modifiable risk factors for this disease.To examine body mass index (BMI) at the age of … Breast cancer is a major cause of mortality among women. It is important to identify modifiable risk factors for this disease.To examine body mass index (BMI) at the age of 18 years and at midlife and adult weight change in relation to breast cancer incidence and mortality.Cohort study.A cohort of 95256 US female nurses aged 30 to 55 years who were followed up for 16 years.Incident and fatal breast cancer.During 1203498 person-years, 2517 incident breast cancers (60% postmenopausal) were documented. Higher current BMI was associated with lower breast cancer incidence before menopause and was minimally associated with incidence after menopause. However, a stronger positive relationship was seen among postmenopausal women who never used hormone replacement (relative risk=1.59 for BMI >31 kg/m2 vs < or = 20 kg/m2; 95% confidence interval, 1.09-2.32; P for trend <.001). Higher BMI at the age of 18 years was associated with lower breast cancer incidence both before and after menopause. Weight gain after the age of 18 years was unrelated to breast cancer incidence before menopause, but was positively associated with incidence after menopause. This increased risk with weight gain was limited to women who never used postmenopausal hormones; among these women, the relative risk was 1.99 (95% confidence interval, 1.43-2.76) for weight gain of more than 20 kg vs unchanged weight (P for trend <.001). Current BMI and weight gain were even more strongly associated with fatal postmenopausal breast cancer. In this population, the percentage of postmenopausal breast cancer accounted for by weight gain alone was approximately 16% and by hormone replacement therapy alone was 5%, but when the interaction between these variables was considered, together they accounted for about one third of postmenopausal breast cancers.Avoiding adult weight gain may contribute importantly to the prevention of breast cancer after menopause, particularly among women who do not use postmenopausal hormones.

Obesity and cancer

2004-08-23

Eugenia E. Calle , Michael J. Thun

Lung Cancer: Epidemiology, Etiology, and Prevention

2011-11-04

Charles S. Dela Cruz , L.T. Tanoue , Richard A. Matthay

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Vegetables, fruit, and cancer. I. Epidemiology

1991-09-01

Kristi A. Steinmetz , John D. Potter

Obesity as a Major Risk Factor for Cancer

2013-01-01

Giovanni De Pergola , Franco Silvestris

The number of cancer cases caused by being obese is estimated to be 20% with the increased risk of malignancies being influenced by diet, weight change, and body fat distribution … The number of cancer cases caused by being obese is estimated to be 20% with the increased risk of malignancies being influenced by diet, weight change, and body fat distribution together with physical activity. Reports from the International Agency for Research into Cancer and the World Cancer Research Fund (WCRF) have shown that the strongest evidence exists for an association of obesity with the following cancer types: endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal, whereas the less common malignancies are leukemia, non-Hodgkin's lymphoma, multiple myeloma, malignant melanoma, and thyroid tumours. To be able to develop novel methods in prevention and treatment, we first must understand the underlying processes which link cancer to obesity. Four main systems have been identified as potential producers of cancer in obesity: insulin, insulin-like growth factor-I, sex steroids, and adipokines. Various novel candidate mechanisms have been proposed: chronic inflammation, oxidative stress, crosstalk between tumour cells and surrounding adipocytes, migrating adipose stromal cells, obesity-induced hypoxia, shared genetic susceptibility, and the functional defeat of immune function. Herein, we review the major pathogenic links between obesity and susceptibility to cancer.

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Abdominal Obesity and the Risk of All-Cause, Cardiovascular, and Cancer Mortality

2008-03-25

Cuilin Zhang , Kathryn M. Rexrode , Rob M. van Dam +2 more

Accumulating evidence indicates that abdominal adiposity is positively related to cardiovascular disease (CVD) risk and some other diseases independently of overall adiposity. However, the association of premature death resulting from … Accumulating evidence indicates that abdominal adiposity is positively related to cardiovascular disease (CVD) risk and some other diseases independently of overall adiposity. However, the association of premature death resulting from these diseases with abdominal adiposity has not been widely studied, and findings are inconsistent.In a prospective cohort study of 44,636 women in the Nurses' Health Study, associations of abdominal adiposity with all-cause and cause-specific mortality were examined. During 16 years of follow-up, 3507 deaths were identified, including 751 cardiovascular deaths and 1748 cancer deaths. After adjustment for body mass index and potential confounders, the relative risks across the lowest to the highest waist circumference quintiles were 1.00, 1.11, 1.17, 1.31, and 1.79 (95% confidence interval [CI], 1.47 to 1.98) for all-cause mortality; 1.00, 1.04, 1.04, 1.28, and 1.99 (95% CI, 1.44 to 2.73) for CVD mortality; and 1.00, 1.18, 1.20, 1.34, and 1.63 (95% CI, 1.32 to 2.01) for cancer mortality (all P<0.001 for trend). Among normal-weight women (body mass index, 18.5 to < 25 kg/m(2)), abdominal obesity was significantly associated with elevated CVD mortality: Relative risk associated with waist circumference > or = 88 cm was 3.02 (95% CI, 1.31 to 6.99) and for waist-to-hip ratio > 0.88 was 3.45 (95% CI, 2.02 to 6.92). After adjustment for waist circumference, hip circumference was significantly and inversely associated with CVD mortality.Anthropometric measures of abdominal adiposity were strongly and positively associated with all-cause, CVD, and cancer mortality independently of body mass index. Elevated waist circumference was associated with significantly increased CVD mortality even among normal-weight women.

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Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial

2009-06-25

Lars Sjöström , Anders Gummesson , C. David Sjöström +7 more

Fasting Insulin and Outcome in Early-Stage Breast Cancer: Results of a Prospective Cohort Study

2002-01-01

Pamela J. Goodwin

PURPOSE: Insulin, a member of a family of growth factors that includes insulin-like growth factor (IGF)-I and IGF-II, exerts mitogenic effects on normal and malignant breast epithelial cells, acting via … PURPOSE: Insulin, a member of a family of growth factors that includes insulin-like growth factor (IGF)-I and IGF-II, exerts mitogenic effects on normal and malignant breast epithelial cells, acting via insulin and IGF-I receptors. Because of this and because of its recognized association with obesity, an adverse prognostic factor in breast cancer, we examined the prognostic associations of insulin in early-stage breast cancer. PATIENTS AND METHODS: A cohort of 512 women without known diabetes, who had early-stage (T1 to T3, N0 to N1, and M0) breast cancer, was assembled and observed prospectively. Information on traditional prognostic factors and body size was collected, and fasting blood was obtained. RESULTS: Fasting insulin was associated with distant recurrence and death; the hazard ratios and 95% confidence intervals (CI) for those in the highest (> 51.9 pmol/L) versus the lowest (< 27.0 pmol/L) insulin quartile were 2.0 (95% CI, 1.2 to 3.3) and 3.1 (95% CI, 1.7 to 5.7), respectively. There was some evidence to suggest that the association of insulin with breast cancer outcomes may be nonlinear. Insulin was correlated with body mass index (Spearman r = 0.59, P < .001), which, in turn, was associated with distant recurrence and death (P < .001). In multivariate analyses that included fasting insulin and available tumor- and treatment-related variables, adjusted hazard ratios for the upper versus lower insulin quartile were 2.1 (95% CI, 1.2 to 3.6) and 3.3 (95% CI, 1.5 to 7.0) for distant recurrence and death, respectively. CONCLUSION: Fasting insulin level is associated with outcome in women with early breast cancer. High levels of fasting insulin identify women with poor outcomes in whom more effective treatment strategies should be explored.

Breastfeeding and maternal health outcomes: a systematic review and meta‐analysis

2015-07-14

Ranadip Chowdhury , Bireshwar Sinha , Mari Jeeva Sankar +5 more

Abstract Aim To evaluate the effect of breastfeeding on long‐term (breast carcinoma, ovarian carcinoma, osteoporosis and type 2 diabetes mellitus) and short‐term (lactational amenorrhoea, postpartum depression, postpartum weight change) maternal … Abstract Aim To evaluate the effect of breastfeeding on long‐term (breast carcinoma, ovarian carcinoma, osteoporosis and type 2 diabetes mellitus) and short‐term (lactational amenorrhoea, postpartum depression, postpartum weight change) maternal health outcomes. Methods A systematic literature search was conducted in PubMed, Cochrane Library and CABI databases. Outcome estimates of odds ratios or relative risks or standardised mean differences were pooled. In cases of heterogeneity, subgroup analysis and meta‐regression were explored. Results Breastfeeding >12 months was associated with reduced risk of breast and ovarian carcinoma by 26% and 37%, respectively. No conclusive evidence of an association between breastfeeding and bone mineral density was found. Breastfeeding was associated with 32% lower risk of type 2 diabetes. Exclusive breastfeeding and predominant breastfeeding were associated with longer duration of amenorrhoea. Shorter duration of breastfeeding was associated with higher risk of postpartum depression. Evidence suggesting an association of breastfeeding with postpartum weight change was lacking. Conclusion This review supports the hypothesis that breastfeeding is protective against breast and ovarian carcinoma, and exclusive breastfeeding and predominant breastfeeding increase the duration of lactational amenorrhoea. There is evidence that breastfeeding reduces the risk of type 2 diabetes. However, an association between breastfeeding and bone mineral density or maternal depression or postpartum weight change was not evident.

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Pooled Analysis of Prospective Cohort Studies on Height, Weight, and Breast Cancer Risk

2000-09-15

Piet A. van den Brandt , Donna Spiegelman , Shiaw Shyuan Yaun +7 more

The association between anthropometric indices and the risk of breast cancer was analyzed using pooled data from seven prospective cohort studies. Together, these cohorts comprise 337,819 women and 4,385 incident … The association between anthropometric indices and the risk of breast cancer was analyzed using pooled data from seven prospective cohort studies. Together, these cohorts comprise 337,819 women and 4,385 incident invasive breast cancer cases. In multivariate analyses controlling for reproductive, dietary, and other risk factors, the pooled relative risk (RR) of breast cancer per height increment of 5 cm was 1.02 (95% confidence interval (CI): 0.96, 1.10) in premenopausal women and 1.07 (95% CI: 1.03, 1.12) in postmenopausal women. Body mass index (BMI) showed significant inverse and positive associations with breast cancer among pre- and postmenopausal women, respectively; these associations were nonlinear. Compared with premenopausal women with a BMI of less than 21 kg/m2, women with a BMI exceeding 31 kg/m2 had an RR of 0.54 (95% CI: 0.34, 0.85). In postmenopausal women, the RRs did not increase further when BMI exceeded 28 kg/m2; the RR for these women was 1.26 (95% CI: 1.09, 1.46). The authors found little evidence for interaction with other breast cancer risk factors. Their data indicate that height is an independent risk factor for postmenopausal breast cancer; in premenopausal women, this relation is less clear. The association between BMI and breast cancer varies by menopausal status. Weight control may reduce the risk among postmenopausal women. Am J Epidemiol 2000;152:514–27.

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Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study

2007-11-06

Gillian Reeves , Kirstin Pirie , Valerie Beral +3 more

Objective To examine the relation between body mass index (kg/m2) and cancer incidence and mortality. Design Prospective cohort study. Participants 1.2 million UK women recruited into the Million Women Study, … Objective To examine the relation between body mass index (kg/m2) and cancer incidence and mortality. Design Prospective cohort study. Participants 1.2 million UK women recruited into the Million Women Study, aged 50-64 during 1996-2001, and followed up, on average, for 5.4 years for cancer incidence and 7.0 years for cancer mortality. Main outcome measures Relative risks of incidence and mortality for all cancers, and for 17 specific types of cancer, according to body mass index, adjusted for age, geographical region, socioeconomic status, age at first birth, parity, smoking status, alcohol intake, physical activity, years since menopause, and use of hormone replacement therapy. Results 45 037 incident cancers and 17 203 deaths from cancer occurred over the follow-up period. Increasing body mass index was associated with an increased incidence of endometrial cancer (trend in relative risk per 10 units=2.89, 95% confidence interval 2.62 to 3.18), adenocarcinoma of the oesophagus (2.38, 1.59 to 3.56), kidney cancer (1.53, 1.27 to 1.84), leukaemia (1.50, 1.23 to 1.83), multiple myeloma (1.31, 1.04 to 1.65), pancreatic cancer (1.24, 1.03 to 1.48), non-Hodgkin9s lymphoma (1.17, 1.03 to 1.34), ovarian cancer (1.14, 1.03 to 1.27), all cancers combined (1.12, 1.09 to 1.14), breast cancer in postmenopausal women (1.40, 1.31 to 1.49) and colorectal cancer in premenopausal women (1.61, 1.05 to 2.48). In general, the relation between body mass index and mortality was similar to that for incidence. For colorectal cancer, malignant melanoma, breast cancer, and endometrial cancer, the effect of body mass index on risk differed significantly according to menopausal status. Conclusions Increasing body mass index is associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined. Among postmenopausal women in the UK, 5% of all cancers (about 6000 annually) are attributable to being overweight or obese. For endometrial cancer and adenocarcinoma of the oesophagus, body mass index represents a major modifiable risk factor; about half of all cases in postmenopausal women are attributable to overweight or obesity.

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Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

2013-06-29

Fedro A. Peccatori , Hatem A. Azim , Roberto Orecchia +4 more

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Dietary Fat Reduction and Breast Cancer Outcome: Interim Efficacy Results From the Women's Intervention Nutrition Study

2006-12-19

Rowan T. Chlebowski , George L. Blackburn , Cynthia A. Thomson +7 more

Preclinical and observational studies suggest a relationship between dietary fat intake and breast cancer, but the association remains controversial. We carried out a randomized, prospective, multicenter clinical trial to test … Preclinical and observational studies suggest a relationship between dietary fat intake and breast cancer, but the association remains controversial. We carried out a randomized, prospective, multicenter clinical trial to test the effect of a dietary intervention designed to reduce fat intake in women with resected, early-stage breast cancer receiving conventional cancer management.A total of 2437 women were randomly assigned between February 1994 and January 2001 in a ratio of 40:60 to dietary intervention (n = 975) or control (n = 1462) groups. An interim analysis was performed after a median follow-up of 60 months when funding for the intervention ceased. Mean differences between dietary intervention and control groups in nutrient intakes and anthropometric variables were compared with t tests. Relapse-free survival was examined using Kaplan-Meier analysis, stratified log-rank tests, and Cox proportional hazards models. Statistical tests were two-sided.Dietary fat intake was lower in the intervention than in the control group (fat grams/day at 12 months, 33.3 [95% confidence interval {CI} = 32.2 to 34.5] versus 51.3 [95% CI = 50.0 to 52.7], respectively; P<.001), corresponding to a statistically significant (P = .005), 6-pound lower mean body weight in the intervention group. A total of 277 relapse events (local, regional, distant, or ipsilateral breast cancer recurrence or new contralateral breast cancer) have been reported in 96 of 975 (9.8%) women in the dietary group and 181 of 1462 (12.4%) women in the control group. The hazard ratio of relapse events in the intervention group compared with the control group was 0.76 (95% CI = 0.60 to 0.98, P = .077 for stratified log rank and P = .034 for adjusted Cox model analysis). Exploratory analyses suggested a differential effect of the dietary intervention based on hormonal receptor status.A lifestyle intervention reducing dietary fat intake, with modest influence on body weight, may improve relapse-free survival of breast cancer patients receiving conventional cancer management. Longer, ongoing nonintervention follow-up will address original protocol design plans, which called for 3 years of follow-up after completion of recruitment.

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Statistical Methods in Cancer Research. Vol. 1 The Analysis of Case‐Control Studies. Herausgegeben von N. E. BRESLOW, N. E. DAY und W. DAVIS. WHO‐IARC Scientific Publications No. 32. 338 Seiten. International Agency for Research on Cancer, Lyon 1980. Preis: 50,‐ sfrs; 30.00 US$

1982-01-01

W. Fritz

Use of chemotherapy during human pregnancy

2004-04-30

Elyce Cardonick , Audrey Iacobucci

Tobacco and Cancer: Recent Epidemiological Evidence

2004-01-20

Paolo Vineis , Michael C.R. Alavanja , Patricia A. Buffler +7 more

Age at first birth and breast cancer risk.

1970-01-01

Brian MacMahon , Philip Cole , T. M. Lin +6 more

An international collaborative study of breast cancer and reproductive experience has been carried out in 7 areas of the world. In all areas studied, a striking relation between age at … An international collaborative study of breast cancer and reproductive experience has been carried out in 7 areas of the world. In all areas studied, a striking relation between age at first birth and breast cancer risk was observed. It is estimated that women having their first child when aged under 18 years have only about one-third the breast cancer risk of those whose first birth is delayed until the age of 35 years or more. Births after the first, even if they occur at an early age, have no, or very little, protective effect. The reduced risk of breast cancer in women having their first child at an early age explains the previously observed inverse relationship between total parity and breast cancer risk, since women having their first birth early tend to become ultimately of high parity. The association with age at first birth requires different kinds of etiological hypotheses from those that have been invoked in the past to explain the association between breast cancer risk and reproductive experience.

Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women

2003-06-24

Rowan T. Chlebowski , Susan L. Hendrix , Robert D. Langer +7 more

ContextThe Women's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks, including invasive breast cancer, exceeded benefits. Outstanding issues not previously addressed include characteristics … ContextThe Women's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks, including invasive breast cancer, exceeded benefits. Outstanding issues not previously addressed include characteristics of breast cancers observed among women using hormones and whether diagnosis may be influenced by hormone effects on mammography.ObjectiveTo determine the relationship among estrogen plus progestin use, breast cancer characteristics, and mammography recommendations.Design, Setting, and ParticipantsFollowing a comprehensive breast cancer risk assessment, 16 608 postmenopausal women aged 50 to 79 years with an intact uterus were randomly assigned to receive combined conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo from 1993 to 1998 at 40 clinical centers. Screening mammography and clinical breast examinations were performed at baseline and yearly thereafter.Main Outcome MeasuresBreast cancer number and characteristics, and frequency of abnormal mammograms by estrogen plus progestin exposure.ResultsIn intent-to-treat analyses, estrogen plus progestin increased total (245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001) and invasive (199 vs 150 cases; HR, 1.24; weighted P = .003) breast cancers compared with placebo. The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P = .04) and were at more advanced stage (regional/metastatic 25.4% vs 16.0%, respectively; P = .04) compared with those diagnosed in the placebo group. After 1 year, the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group (716 [9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001), a pattern which continued for the study duration.ConclusionsRelatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms. These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis.

Epidemiology of breast cancer

2001-03-01

Timothy J. Key , Pia K. Verkasalo , Emily Banks

Body mass index and survival in women with breast cancer—systematic literature review and meta-analysis of 82 follow-up studies

2014-04-28

Doris S. M. Chan , Ana Vieira , Dagfinn Aune +7 more

Positive association between obesity and survival after breast cancer was demonstrated in previous meta-analyses of published data, but only the results for the comparison of obese versus non-obese was summarised.We … Positive association between obesity and survival after breast cancer was demonstrated in previous meta-analyses of published data, but only the results for the comparison of obese versus non-obese was summarised.We systematically searched in MEDLINE and EMBASE for follow-up studies of breast cancer survivors with body mass index (BMI) before and after diagnosis, and total and cause-specific mortality until June 2013, as part of the World Cancer Research Fund Continuous Update Project. Random-effects meta-analyses were conducted to explore the magnitude and the shape of the associations.Eighty-two studies, including 213 075 breast cancer survivors with 41 477 deaths (23 182 from breast cancer) were identified. For BMI before diagnosis, compared with normal weight women, the summary relative risks (RRs) of total mortality were 1.41 [95% confidence interval (CI) 1.29-1.53] for obese (BMI >30.0), 1.07 (95 CI 1.02-1.12) for overweight (BMI 25.0-<30.0) and 1.10 (95% CI 0.92-1.31) for underweight (BMI <18.5) women. For obese women, the summary RRs were 1.75 (95% CI 1.26-2.41) for pre-menopausal and 1.34 (95% CI 1.18-1.53) for post-menopausal breast cancer. For each 5 kg/m(2) increment of BMI before, <12 months after, and ≥12 months after diagnosis, increased risks of 17%, 11%, and 8% for total mortality, and 18%, 14%, and 29% for breast cancer mortality were observed, respectively.Obesity is associated with poorer overall and breast cancer survival in pre- and post-menopausal breast cancer, regardless of when BMI is ascertained. Being overweight is also related to a higher risk of mortality. Randomised clinical trials are needed to test interventions for weight loss and maintenance on survival in women with breast cancer.

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Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies

2008-02-01

Andrew G. Renehan , Margaret Tyson , Matthias Egger +2 more

Obesity and Cancer

2010-05-27

Kathleen Y. Wolin , Kenneth R. Carson , Graham A. Colditz

Abstract Weight, weight gain, and obesity account for approximately 20% of all cancer cases. Evidence on the relation of each to cancer is summarized, including esophageal, thyroid, colon, renal, liver, … Abstract Weight, weight gain, and obesity account for approximately 20% of all cancer cases. Evidence on the relation of each to cancer is summarized, including esophageal, thyroid, colon, renal, liver, melanoma, multiple myeloma, rectum, gallbladder, leukemia, lymphoma, and prostate in men; and postmenopausal breast and endometrium in women. Different mechanisms drive etiologic pathways for these cancers. Weight loss, particularly among postmenopausal women, reduces risk for breast cancer. Among cancer patients, data are less robust, but we note a long history of poor outcomes after breast cancer among obese women. While evidence on obesity and outcomes for other cancers is mixed, growing evidence points to benefits of physical activity for breast and colon cancers. Dosing of chemotherapy and radiation therapy among obese patients is discussed and the impact on therapy-related toxicity is noted. Guidelines for counseling patients for weight loss and increased physical activity are presented and supported by strong evidence that increased physical activity leads to improved quality of life among cancer survivors. The “Five A's” model guides clinicians through a counseling session: assess, advise, agree, assist, arrange. The burden of obesity on society continues to increase and warrants closer attention by clinicians for both cancer prevention and improved outcomes after diagnosis.

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Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults

2014-08-01

Krishnan Bhaskaran , Ian Douglas , Harriet Forbes +3 more

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Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies

2012-10-17

Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects … Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women.Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression.Breast cancer risk increased by a factor of 1·050 (95% CI 1·044-1·057; p<0·0001) for every year younger at menarche, and independently by a smaller amount (1·029, 1·025-1·032; p<0·0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1·43, 1·33-1·52, p<0·001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p<0·006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p<0·01 for both comparisons).The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours.Cancer Research UK.

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Global burden of cancer attributable to high body-mass index in 2012: a population-based study

2014-11-25

Melina Arnold , Nirmala Pandeya , Graham Byrnes +7 more

High body-mass index (BMI; defined as 25 kg/m(2) or greater) is associated with increased risk of cancer. To inform public health policy and future research, we estimated the global burden … High body-mass index (BMI; defined as 25 kg/m(2) or greater) is associated with increased risk of cancer. To inform public health policy and future research, we estimated the global burden of cancer attributable to high BMI in 2012.

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Reproductive Factors and Breast Cancer

1993-01-01

Jennifer L. Kelsey , Marilie D. Gammon , Esther M. John

Journal Article Reproductive Factors and Breast Cancer Get access Jennifer L. Kelsey, Jennifer L. Kelsey 1Stanford University School of MedicineStanford, CA Dr. Jennifer L. Kelsey, Division of Epidemiology, Department of … Journal Article Reproductive Factors and Breast Cancer Get access Jennifer L. Kelsey, Jennifer L. Kelsey 1Stanford University School of MedicineStanford, CA Dr. Jennifer L. Kelsey, Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine, Health Research and Policy Building, Stanford, CA 94305-5092 Search for other works by this author on: Oxford Academic PubMed Google Scholar Marilie D. Gammon, Marilie D. Gammon 2Columbia University School of Public HealthNew York, NY Search for other works by this author on: Oxford Academic PubMed Google Scholar Esther M. John Esther M. John 1Stanford University School of MedicineStanford, CA Search for other works by this author on: Oxford Academic PubMed Google Scholar Epidemiologic Reviews, Volume 15, Issue 1, 1993, Pages 36–47, https://doi.org/10.1093/oxfordjournals.epirev.a036115 Published: 01 March 1993 Article history Received: 18 November 1992 Revision received: 25 February 1993 Published: 01 March 1993

Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52 705 women with breast cancer and 108 411 women without breast cancer

1997-10-01

Background. The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed about 90% of the worldwide epidemiological evidence on the relation between risk of breast cancer … Background. The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed about 90% of the worldwide epidemiological evidence on the relation between risk of breast cancer and use of hormone replacement therapy (HRT). Methods. Individual data on 52,705 women with breast cancer and 108,411 women without breast cancer from 51 studies in 21 countries were collected, checked, and analysed centrally. The main analyses are based on 53,865 postmenopausal women with a known age at menopause, of whom 17,830 (33%) had used HRT at some time. The median age at first use was 48 years, and 34% of ever-users had used HRT for 5 years or longer. Estimates of the relative risk of breast cancer associated with the use of HRT were obtained after stratification of all analyses by study, age at diagnosis, time since menopause, body-mass index, parity, and the age a woman was when her first child was born. Findings. Among current users of HRT or those who ceased use 1-4 years previously, the relative risk of having breast cancer diagnosed increased by a factor of 1.023 (95% CI 1.011-1.036; 2p = 0.0002) for each year of use; the relative risk was 1.35 (1.21-1.49; 2p = 0.00001) for women who had used HRT for 5 years or longer (average duration of use in this group 11 years). This increase is comparable with the effect on breast cancer of delaying menopause, since among never-users of HRT the relative risk of breast cancer increases by a factor of 1.028 (95% CI 1.021-1.034) for each year older at menopause. 5 or more years after cessation of HRT use, there was no significant excess of breast cancer overall or in relation to duration of use. These main findings did not vary between individual studies. Of the many factors examined that might affect the relation between breast cancer risk and use of HRT, only a woman's weight and body-mass index had a material effect: the increase in the relative risk of breast dancer associated with long durations of use in current and recent users was greater for women of lower than of higher weight or body-mass index. There was no marked variation in the results according to hormonal type or dose but little information was available about long durations of use of any specific preparation. Cancers diagnosed in women who had ever used HRT tended to be less advanced clinically than those diagnosed in never-users. In North America and Europe the cumulative incidence of breast cancer between the ages of 50 and 70 in never-users of HRT is about 45 per 1000 women. The cumulative excess numbers of breast cancers diagnosed between these ages per 1000 women who began use of HRT at age 50 and used it for 5, 10, and 15 years, respectively, are estimated to be 2 (95% CI 1-3), 6 (3-9), and 12 (5-20). Whether HRT affects mortality from breast cancer is not known. Interpretation. The risk of having breast cancer diagnosed is increased in women using HRT and increases with increasing duration of use. This effect is reduced after cessation of use of HRT and has largely, if not wholly, disappeared after about 5 years. These findings should be considered in the context of the benefits and other risks associated with the use of HRT.

The fractions of cancer attributable to modifiable factors: A global review

2016-07-26

David C. Whiteman , Louise F. Wilson

Body Fatness and Cancer — Viewpoint of the IARC Working Group

2016-08-24

Béatrice Secretan , Chiara Scoccianti , Dana Loomis +3 more

The International Agency for Research on Cancer convened a workshop on the relationship between body fatness and cancer, from which an IARC handbook on the topic will appear. An executive … The International Agency for Research on Cancer convened a workshop on the relationship between body fatness and cancer, from which an IARC handbook on the topic will appear. An executive summary of the evidence is presented.

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Low-Fat Dietary Pattern and Risk of Invasive Breast Cancer

2006-02-07

Ross L. Prentice , Bette J. Caan , Rowan T. Chlebowski +7 more

The hypothesis that a low-fat dietary pattern can reduce breast cancer risk has existed for decades but has never been tested in a controlled intervention trial.To assess the effects of … The hypothesis that a low-fat dietary pattern can reduce breast cancer risk has existed for decades but has never been tested in a controlled intervention trial.To assess the effects of undertaking a low-fat dietary pattern on breast cancer incidence.A randomized, controlled, primary prevention trial conducted at 40 US clinical centers from 1993 to 2005.A total of 48,835 postmenopausal women, aged 50 to 79 years, without prior breast cancer, including 18.6% of minority race/ethnicity, were enrolled.Women were randomly assigned to the dietary modification intervention group (40% [n = 19,541]) or the comparison group (60% [n = 29,294]). The intervention was designed to promote dietary change with the goals of reducing intake of total fat to 20% of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily. Comparison group participants were not asked to make dietary changes.Invasive breast cancer incidence.Dietary fat intake was significantly lower in the dietary modification intervention group compared with the comparison group. The difference between groups in change from baseline for percentage of energy from fat varied from 10.7% at year 1 to 8.1% at year 6. Vegetable and fruit consumption was higher in the intervention group by at least 1 serving per day and a smaller, more transient difference was found for grain consumption. The number of women who developed invasive breast cancer (annualized incidence rate) over the 8.1-year average follow-up period was 655 (0.42%) in the intervention group and 1072 (0.45%) in the comparison group (hazard ratio, 0.91; 95% confidence interval, 0.83-1.01 for the comparison between the 2 groups). Secondary analyses suggest a lower hazard ratio among adherent women, provide greater evidence of risk reduction among women having a high-fat diet at baseline, and suggest a dietary effect that varies by hormone receptor characteristics of the tumor.Among postmenopausal women, a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1-year average follow-up period. However, the nonsignificant trends observed suggesting reduced risk associated with a low-fat dietary pattern indicate that longer, planned, nonintervention follow-up may yield a more definitive comparison.ClinicalTrials.gov Identifier: NCT00000611.

Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention

2017-08-01

Manuel Picon‐Ruiz , Cynthia Morata‐Tarifa , Janeiro J. Valle‐Goffin +2 more

Abstract Answer questions and earn CME/CNE Recent decades have seen an unprecedented rise in obesity, and the health impact thereof is increasingly evident. In 2014, worldwide, more than 1.9 billion … Abstract Answer questions and earn CME/CNE Recent decades have seen an unprecedented rise in obesity, and the health impact thereof is increasingly evident. In 2014, worldwide, more than 1.9 billion adults were overweight (body mass index [BMI], 25‐29.9 kg/m 2 ), and of these, over 600 million were obese (BMI ≥30 kg/m 2 ). Although the association between obesity and the risk of diabetes and coronary artery disease is widely known, the impact of obesity on cancer incidence, morbidity, and mortality is not fully appreciated. Obesity is associated both with a higher risk of developing breast cancer, particularly in postmenopausal women, and with worse disease outcome for women of all ages. The first part of this review summarizes the relationships between obesity and breast cancer development and outcomes in premenopausal and postmenopausal women and in those with hormone receptor‐positive and ‐negative disease. The second part of this review addresses hypothesized molecular mechanistic insights that may underlie the effects of obesity to increase local and circulating proinflammatory cytokines, promote tumor angiogenesis and stimulate the most malignant cancer stem cell population to drive cancer growth, invasion, and metastasis. Finally, a review of observational studies demonstrates that increased physical activity is associated with lower breast cancer risk and better outcomes. The effects of recent lifestyle interventions to decrease sex steroids, insulin/insulin‐like growth factor‐1 pathway activation, and inflammatory biomarkers associated with worse breast cancer outcomes in obesity also are discussed. Although many observational studies indicate that exercise with weight loss is associated with improved breast cancer outcome, further prospective studies are needed to determine whether weight reduction will lead to improved patient outcomes. It is hoped that several ongoing lifestyle intervention trials, which are reviewed herein, will support the systematic incorporation of weight loss intervention strategies into care for patients with breast cancer. CA Cancer J Clin 2017;67:378–397. © 2017 The Authors. CA A Cancer Journal for Clinicians published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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Obesity and cancer risk: Emerging biological mechanisms and perspectives

2018-11-13

Konstantinos Avgerinos , Nikolaos Spyrou , Christos S. Mantzoros +1 more

Adenocarcinoma of the Vagina

1971-04-22

Arthur L. Herbst , Howard Ulfelder , David C. Poskanzer

Adenocarcinoma of the vagina in young women had been recorded rarely before the report of several cases treated at the Vincent Memorial Hospital between 1966 and 1969. The unusual occurrence … Adenocarcinoma of the vagina in young women had been recorded rarely before the report of several cases treated at the Vincent Memorial Hospital between 1966 and 1969. The unusual occurrence of this tumor in eight patients born in New England hospitals between 1946 and 1951 led us to conduct a retrospective investigation in search of factors that might be associated with tumor appearance. Four matched controls were established for each patient; data were obtained by personal interview. Results show maternal bleeding during the current pregnancy and previous pregnancy loss were more common in the study group. Most significantly, seven of the eight mothers of patients with carcinoma had been treated with diethylstilbestrol started during the first trimester. None in the control group were so treated (p less than 0.00001). Maternal ingestion of stilbestrol during early pregnancy appears to have enhanced the risk of vaginal adenocarcinoma developing years later in the offspring exposed.

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Key steps for effective breast cancer prevention

2020-06-11

Kara L. Britt , Jack Cuzick , Kelly‐Anne Phillips

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Breast cancer and hormone-replacement therapy: the Million Women Study

2003-10-01

Valerie Beral , Emily Banks , Gillian Reeves +1 more

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[Principles and practice of mass screening for disease].

1968-10-01

J M Wilson , Y G Jungner

Smoking and Lung Cancer: Recent Evidence and a Discussion of Some Questions

1959-01-01

Jerome Cornfield , William Haenszel , Edward Hammond +3 more

Journal Article Smoking and Lung Cancer: Recent Evidence and a Discussion of Some Questions Get access Jerome Cornfield, Jerome Cornfield Search for other works by this author on: Oxford Academic … Journal Article Smoking and Lung Cancer: Recent Evidence and a Discussion of Some Questions Get access Jerome Cornfield, Jerome Cornfield Search for other works by this author on: Oxford Academic PubMed Google Scholar William Haenszel, William Haenszel Search for other works by this author on: Oxford Academic PubMed Google Scholar E. Cuyler Hammond, E. Cuyler Hammond Search for other works by this author on: Oxford Academic PubMed Google Scholar Abraham M. Lilienfeld, Abraham M. Lilienfeld Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael B. Shimkin, Michael B. Shimkin Search for other works by this author on: Oxford Academic PubMed Google Scholar Ernst L. Wynder Ernst L. Wynder Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 22, Issue 1, January 1959, Pages 173–203, https://doi.org/10.1093/jnci/22.1.173 Published: 01 January 1959 Article history Received: 15 October 1958 Published: 01 January 1959

Association of anthropometric indices with rs9939609 FTO gene polymorphism among overweight/obese women with breast cancer: a case-control study

2025-06-24

Huma Naqeeb , Bismillah Sehar , Sami Siraj +7 more | Frontiers in Nutrition

Background/objectives Fat mass and obesity associated (FTO) gene and anthropometric measurements might be associated with breast cancer (BC) risk. This study aimed to assess the interactions between single nucleotide polymorphism … Background/objectives Fat mass and obesity associated (FTO) gene and anthropometric measurements might be associated with breast cancer (BC) risk. This study aimed to assess the interactions between single nucleotide polymorphism (SNP) rs9939609 of the FTO gene, anthropometric indices, and BC risk among pre- and post-menopause women with overweight/obesity in Pakistan. Methods This retrospective case–control study conducted on a convenience sample of 200 women divided into two groups: a case group comprised of 100 women diagnosed with BC, and control group comprised of 100 (age and menopausal status matched healthy women). Physical activity was assessed using validated questionnaire. Data on body mass index (BMI, kg/m2), waist-to-hip ratio (WHR, cm), sociodemographic, and blood samples were collected from both groups. The rs9939609 FTO gene polymorphism was genotyped using the tetra-primer amplification refractory mutation system polymerase chain reaction and Sanger sequencing. Multiple regressions were presented as adjusted odds ratios (OR) and their respective confidence intervals (95% CI). Results The FTO rs9939609 T &gt; A polymorphism showed a significantly higher frequency of the homozygous AA genotype in BC patients compared to healthy controls (22% vs. 13%, p &lt; 0.05). The odds ratio for BC was 2.4 (CI = 1.09–5.3, p &lt; 0.05), indicating that women with the AA genotype were more susceptible to BC compared to those with the wild-type TT genotype. Additionally, BC patients exhibited significantly higher BMI (27 ± 4.0 vs. 25 ± 3.4, p &lt; 0.05) and WHR (0.88 ± 0.06 vs. 0.85 ± 0.08, p &lt; 0.05) compared to healthy controls. These findings suggest a significant association between the FTO rs9939609 AA genotype, obesity, and BC risk. Conclusion FTO gene polymorphism may be implicated in the etiopathogenesis of BC, both in FTO pre- and post-menopause women diagnosed with overweight/obesity. Future cohorts are required to confirm the association between the FTO gene and BC in obese women and to identify the underlying biological mechanisms.

Breast Density and Volume Changes During the Menstrual Cycle

2025-06-24

TeAyra Dillard , J. T. Jones , B. Bernard +4 more | Advances in General Practice of Medicine

This paper explores the dynamic changes in breast moisture content in relation to hormonal fluctuations throughout the menstrual cycle, emphasizing the role of estrogen and progesterone in influencing breast physiology. … This paper explores the dynamic changes in breast moisture content in relation to hormonal fluctuations throughout the menstrual cycle, emphasizing the role of estrogen and progesterone in influencing breast physiology. The menstrual cycle is divided into four phases—menstrual, follicular, ovulatory, and luteal—each of which elicits measurable variations in breast volume, density, and moisture due to hormone-driven tissue remodeling and fluid retention. Estrogen predominates in the follicular phase, promoting ductal proliferation and mild fluid accumulation, while the luteal phase is characterized by a significant rise in progesterone, resulting in marked stromal edema, increased glandular development, and heightened fluid retention. These hormonal changes are mediated through the renin-angiotensin-aldosterone system (RAAS) and vasopressin pathways, which contribute to systemic and localized water retention, especially within breast tissue. The paper synthesizes hormonal biochemistry, breast anatomy, and biomechanical modeling to examine how these cyclic changes impact breast density and volume, with clinical implications for breast tenderness, mammographic sensitivity, and cancer screening. Imaging data and statistical analyses reveal a consistent pattern of increased breast density and volume during the luteal phase. Understanding these cyclical changes enhances the ability to anticipate breast-related symptoms, improve diagnostic timing, and personalize care, particularly for women with dense breast tissue or hormone-sensitive conditions.

Uterine volume assay after gonadotoxic therapies in childhood, adolescence, and young adulthood: A systematic review and Bayesian network meta‐analysis

2025-06-24

Éloïse Fraison , S. Huberlant , Mathilde Cavalieri +4 more | Acta Obstetricia Et Gynecologica Scandinavica

Abstract Introduction Uterine damage after pelvic radiotherapy or total‐body irradiation is well described, with decreased uterine volume and high obstetrical morbidity. Some recent studies have reported a smaller uterus in … Abstract Introduction Uterine damage after pelvic radiotherapy or total‐body irradiation is well described, with decreased uterine volume and high obstetrical morbidity. Some recent studies have reported a smaller uterus in child, adolescent, and young adult cancer survivors treated with chemotherapy only. This systematic review investigated the long‐term effects of gonadotoxic therapy on uterine volume during childhood, adolescence, and young adulthood. Material and Methods Data sources were Medline, Embase, and the Cochrane Library databases from 1990 to April 2023 searched using the following search terms: cancer survivors, bone marrow transplantation, chemotherapy, radiotherapy, and uterine volume. Study selection and synthesis: Only comparative studies reporting uterine volume in adult women who had received chemotherapy and/or radiotherapy during childhood, adolescence, or young adulthood (<25 years) were included. Two independent reviewers performed study selection, bias assessment using the ROBINS‐I tool, and data extraction. The main outcome was uterine volume (mL). A Bayesian network meta‐analysis with meta‐regression for parity and serious risk of bias was performed using a random‐effects model. Results After reviewing 2847 abstracts, four studies were selected for the meta‐analysis. Uterine volume data were available for 225 women after chemotherapy, 153 women after chemoradiotherapy, and 257 control women without cancer. Uterine volume was significantly lower in the chemoradiotherapy group than in the control group (−29.2 mL [−49.1, −12.5]). Uterine volume was significantly decreased in the chemoradiotherapy group compared to the chemotherapy group (−20.9 mL [−39.1, −0.3]). The difference in the mean uterine volume between the control and chemotherapy groups was 8.2 mL [−11.8, 34.2] and was not significant. Conclusions Our meta‐analysis confirms the well‐known data on chemoradiotherapy‐induced uterine damage. Although some studies have suggested the potential impact of high doses of chemotherapy on uterine volume, this meta‐analysis did not find any significant decrease in uterine volume after chemotherapy. This result could help counsel age‐reproductive women and physicians who perform assisted reproductive technologies in long‐term CAYA Cancer survivors.

Efeito do Álcool na Tomada de Decisão: Potencial Impacto na Detecção Precoce do Câncer

2025-06-24

Jainne Martins Ferreira , Adriana Tavares de Moraes Atty , Laura Mello Schmidt +1 more | Revista Brasileira de Cancerologia

O álcool é um importante fator de risco para várias doenças crônicas, entre elas, o câncer. Mas, para além dos estudos sobre ação carcinogênica do álcool, verifica-se a necessidade de … O álcool é um importante fator de risco para várias doenças crônicas, entre elas, o câncer. Mas, para além dos estudos sobre ação carcinogênica do álcool, verifica-se a necessidade de estudos que se concentrem nos efeitos do álcool no âmbito da neurociência cognitiva e o impacto nas ações voltadas tanto para a cessação do consumo quanto em estratégias de detecção precoce do câncer. O uso crônico do álcool promove alterações estruturais e funcionais que perduram e implicam em prejuízos na rede de conexão estabelecidas entre o córtex pré-frontal e outras áreas corticais, bem como com regiões subcorticais, que podem resultar em comprometimento das habilidades multitarefa, refletindo déficits na memória de trabalho. Essa disfunção cognitiva se relaciona com um padrão de tomada de decisão de alto risco, sugerindo uma ligação entre a capacidade da memória de trabalho e a propensão a escolhas arriscadas nesses indivíduos. E, por conseguinte, pressupõe-se que o comprometimento cognitivo causado pelo álcool pode prejudicar a identificação dos sinais de alerta para alguns tipos de câncer e afetar a capacidade de tomada de decisão em buscar os serviços de saúde.

The First 6 Years’ Experiences of a National Centralized Offspring Surveillance Setting for Dutch Children Prenatally Exposed to Maternal Cancer to Inform Future International Practice: Protocol for a Demographic Review of Referred Families and Key Lessons Learned

2025-06-24

Evangeline A. Huis in ’t Veld , Aksel Kruse , Emma J. Verwaaijen +7 more | JMIR Research Protocols

Background Cancer during pregnancy is a rare and significant life-changing event affecting approximately 1 in 1000-2000 pregnancies. With increasing maternal age and broader application of prenatal screening programs such as … Background Cancer during pregnancy is a rare and significant life-changing event affecting approximately 1 in 1000-2000 pregnancies. With increasing maternal age and broader application of prenatal screening programs such as the Dutch Non-Invasive Prenatal Testing, incidental detection of maternal cancer is becoming more frequent. Advancements in safe treatment options during pregnancy, supported by the International Network on Cancer Infertility and Pregnancy (INCIP), have led to fewer pregnancy terminations. Consequently, more children are exposed to chemotherapy and other cancer treatments in utero. While short-term safety has been demonstrated for many oncological agents, long-term side effects including physical, neuromotor, neurocognitive, and psychosocial impacts on offspring and their families after delivery are still being assessed. Standard settings for surveillance and care of offspring and their families have, however, never been described. Objective Given the importance of expertise in assessing the long-term outcomes of children, the Netherlands established the national centralized Cancer in Pregnancy (CIP) offspring outpatient clinic in 2018, which functions as a standard-of-care surveillance clinic and contributes data to the INCIP registry. Here we provide a demographic overview of referred families and to share (logistic) experiences with the national, centralized, multidisciplinary, and standardized long-term surveillance program for all Dutch children with in utero exposure to maternal cancer and its treatment. Methods The CIP offspring outpatient clinic is located at the Princess Máxima Center for Pediatric Oncology and provides surveillance from infancy until 18 years of age. The, relatively small dedicated team, comprising pediatric oncologists, physiotherapists, and a psychological expert, offers a 1-day, multidisciplinary assessment, including physical examinations, neuromotor tests, cardiac monitoring (for anthracycline exposure), renal and auditory screening (for platinum agents), neurocognitive testing, and psychosocial evaluation. Surveillance is aligned with international INCIP guidelines. Results From May 2018 to 2024, a total of 226 children (from 221 mothers) have been referred to the CIP offspring outpatient clinic, with 465 follow-up visits completed. The most common maternal cancer types were breast, gynecological, and hematological malignancies. Most women (58%) received chemotherapy during pregnancy; 11% of them had surgery only, 3% underwent radiotherapy, 3% underwent immunotherapy, 16% received a combination of treatment modalities, and 8% did not undergo treatment during pregnancy. Anthracyclines were the most commonly used agents. Median gestational age at delivery was 37.3 weeks. Fourteen percent of the mothers died shortly after delivery, underscoring the emotional and logistical challenges for families. Conclusions The CIP offspring outpatient clinic provides a unique, structured approach to long-term surveillance for in utero–exposed children, which enables early detection of potential late effects and provides comprehensive family support. By sharing knowledge and experiences from the unique setting of this national centralized CIP offspring outpatient clinic, this initiative may inspire other countries in developing similar translational facilities to support affected families and improve care worldwide. International Registered Report Identifier (IRRID) DERR1-10.2196/71612

Navigating Oral Cancers in Pregnancy: A Systematic Review of Management and Outcomes

2025-06-24

M. Troconis , Shahme Farook | International Journal of Oral and Maxillofacial Surgery

Assessing Clinicopathologic and Prognostic Factors in Pregnancy-Associated Breast Cancer: The Role of Timing, Age, and Parity

2025-06-23

M. Elgendy , Nourhan Abdalkader , Ahmed S. Elsayed +2 more | Research Square (Research Square)

<title>Abstract</title> This study explores the pathological, clinical, and prognostic characteristics of pregnancy-associated breast cancer (PABC). Our findings challenge specific biological models by revealing no significant differences in local nodal involvement, … <title>Abstract</title> This study explores the pathological, clinical, and prognostic characteristics of pregnancy-associated breast cancer (PABC). Our findings challenge specific biological models by revealing no significant differences in local nodal involvement, lymphovascular invasion, pathological type, or hormone receptor status between the pregnancy and postpartum groups. Additionally, recurrence-free survival results revealed worse results in the postpartum group compared to the pregnancy group, this disparity did not reach statistical significance. These results align with existing evidence but contradict findings from biological models.

Obesity and breast cancer: exploring the nexus of chronic inflammation, metabolic dysregulation, and nutritional strategies

2025-06-23

Claudia Reytor-González , Daniel Simancas‐Racines , Náthaly Mercedes Román-Galeano +7 more | Food and Agricultural Immunology

Area deprivation index and breast cancer outcomes among patients in Western New York

2025-06-22

Malak Alharbi , Jayasree Krishnan , Arya Mariam Roy +7 more | Breast Cancer Research and Treatment

Several studies have shown that residing in regions with high area deprivation index (ADI) is associated with worse outcomes. We evaluated associations between ADI and breast cancer (BC) outcomes among … Several studies have shown that residing in regions with high area deprivation index (ADI) is associated with worse outcomes. We evaluated associations between ADI and breast cancer (BC) outcomes among patients in Western New York (WNY), a region that includes multiple underserved areas. This retrospective, single-institution study analyzed data from 404 BC patients diagnosed between 2014 and 2018. Demographic and clinicopathological data were abstracted. Data were compared between high (≥ 60) and low (< 60) ADI groups, reflective of high and low levels of socioeconomic disadvantage, respectively. The primary objective was overall survival (OS) by ADI. Secondary objectives included assessment of recurrence free survival (RFS) or time to next treatment (TNT) by ADI and frequency of germline and somatic testing. Over half of the patients (59%) resided in ADI ≥ 60. 77% of patients had stage I-III BC and 23% had de novo metastatic BC. Patients in ADI ≥ 60 had a lower 5-year OS rate (73%) than those in ADI < 60 (84%) (95%CI: 67.5-79.7, P = 0.05). In multivariable analysis, similar trend was observed but was not statistically significant (HR 1.56, 95%CI: 0.98-2.46, P = 0.058). There were no differences in TNT or RFS by ADI. Germline testing was performed less frequently (33%) in ADI ≥ 60 than ADI < 60 group (45%) (P = 0.04) for patients with stage I-III BC, while no difference observed for stage IV patients. Finally, prevalence of somatic mutations in TP53, PIK3CA, and ESR1 were higher in ADI ≥ 60. We observed a trend towards worse OS in areas with high ADI, though not statistically significant. The incidence of germline testing was lower in high ADI compared to low ADI regions.

The Role of BMI and TNF-α in Breast Cancer Development: A Case‒Control Study

2025-06-22

Shen Wang , Y. Li , Hengming Ye +1 more | Archives of Medical Science

Introduction A high body mass index (BMI) is closely linked to increased breast cancer risk. Despite the established links between BMI and TNF-α with breast cancer, few studies have explored … Introduction A high body mass index (BMI) is closely linked to increased breast cancer risk. Despite the established links between BMI and TNF-α with breast cancer, few studies have explored their combined effects on breast cancer development. The aim of our study was to evaluate the separate and combined associations of BMI and tumor necrosis factor-alpha (TNF-α) with breast cancer risk. Material and methods This study conducted a case‒control analysis involving 794 women diagnosed with breast cancer and 268 age‒matched healthy controls from Sun Yat-sen University's affiliated hospitals between October 2008 and March 2018. Data on demographic characteristics, clinical features, and TNF-α levels were collected. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between BMI, TNF-α, and breast cancer risk. Results High levels of TNF-α (≥58.45 µg/ml) were significantly associated with an increased risk of breast cancer (OR 1.500; 95% CI 1.112–2.022). Elevated TNF-α levels are linked to early clinical stage, ER-positive, PR-positive, HER2-positive, high Ki67 expression, and the absence of lymphatic and distant metastases. No significant association was found between BMI and breast cancer risk (OR 0.947; 95% CI 0.685–1.310), nor was there a significant interaction effect between BMI and TNF-α. Conclusions TNF-α plays a significant role in breast cancer development, particularly in early clinical stages, and in specific pathological features. BMI alone is not a significant predictor of breast cancer risk. These findings underscore the importance of TNF-α as a potential target for breast cancer prevention and treatment strategies.

Response to Letter to the Editor - Breast Cancer Characteristics after Metabolic and Bariatric Surgery: A Matched Comparison to Patients with Severe Obesity

2025-06-21

Adam Abu-Abeid , Jawad Tome , Marian Khatib | Obesity Surgery

Fibrosis- 4 index and survival in early breast cancer patients

2025-06-20

Onur Baş , Mert Tokatlı , Naciye Güdük +3 more | Acta Medica

Background: The objective of this study is to assess the correlation between survival outcomes and fibrosis-4 (FIB-4) index in patients with non-metastatic breast cancer treated with anthracyclines Methods: This study … Background: The objective of this study is to assess the correlation between survival outcomes and fibrosis-4 (FIB-4) index in patients with non-metastatic breast cancer treated with anthracyclines Methods: This study was conducted on individuals with non-metastatic breast cancer who were treated with at least one dose of anthracycline from 2018 to 2023. The FIB-4 index was calculated based on the following parameters: age, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) serum levels, and platelet count for each patient before anthracycline treatment. Results: A total of 208 patients were included in the study. Patients below 35 years of age (n=28) and those above 65 years of age (n=11) were excluded from the study as the FIB-4 index is less reliable in these age groups. Patients were then divided into two subgroups, low and high, according to the pre-defined cut-off value of 1.45, which is obtained from the primary reference. In univariate analysis, hemoglobin (p=0.03), FIB-4 index (p=0.02), and diagnosis at stage (p=0.01) were statistically related to overall survival (OS). In multivariate analysis, patients with higher FIB-4 index (HR: 4.36, 95% CI 1.38-13.78 p=0.012), anemia (HR: 3.32, 95% CI 1.32-8.34, p=0.011), and stage 3 (HR: 4.53, 95% CI 1.22-16.76, p=0.024) had decreased OS. An additional aim was to evaluate the association between anthracycline-induced cardiotoxicity and the FIB-4 index. Our study showed no relationship (p=0.738). Conclusions: The FIB-4 index, a marker easily obtained through routine biochemistry testing at low cost, could serve as an independent predictor of OS patients with non-metastatic breast cancer treated with anthracyclines. Routine lab tests performed for cancer patients may help clinicians identify high-risk patients in whom closer follow-up or protective measures should be considered.

Reproductive decision-making and pregnancy in germlineCDH1variant carriers

2025-06-20

Amber F. Gallanis , Cassidy Bowden , Rachael Lopez +6 more | Journal of Medical Genetics

Background Diagnosis of a hereditary cancer syndrome may impact family planning, particularly in reproductive age individuals. Factors influencing reproductive decision-making are understudied in individuals with germline CDH1 pathogenic or likely … Background Diagnosis of a hereditary cancer syndrome may impact family planning, particularly in reproductive age individuals. Factors influencing reproductive decision-making are understudied in individuals with germline CDH1 pathogenic or likely pathogenic (P/LP) variants. Methods We characterised reproductive decision-making and perinatal outcomes in 121 individuals aged 18–49 with hereditary diffuse gastric and lobular breast cancer syndrome due to a germline CDH1 P/LP variant. Results Half of individuals (50%, 60/121) reported their CDH1 diagnosis impacted family planning. Psychosocial and economic barriers to reproduction were encountered by 47% (56/119) of patients. Additionally, 12% (15/121) of individuals delayed pregnancy to prioritise personal cancer risk management with either endoscopic surveillance, prophylactic total gastrectomy (PTG) or mastectomy. Women were more likely to experience guilt about passing their CDH1 variant to offspring compared with men. Perinatal and fetal outcomes were investigated in six women who gave birth at a median time of 24 months (IQR 20–44) after PTG. Maternal micronutrient deficiencies were not uncommon in pregnant women after PTG despite compliance with a bariatric, prenatal multivitamin. Majority of women who became pregnant after PTG reported worsening post-gastrectomy syndromes. Most infants (90%, 9/10) born after PTG were full-term and no fetal complications were reported. Conclusion Reproductive decision-making is complex in individuals with germline CDH1 variants, who often encounter psychosocial and physical challenges during family planning and pregnancy. However, successful pregnancy is possible after PTG with the guidance of a multidisciplinary team including maternal fetal medicine specialists and a registered dietitian. Trial registration number NCT03030404 .

The Relationship Between Obesity and Cancer: Epidemiology, Pathophysiology, and the Effect of Obesity Treatment on Cancer

2025-06-19

Yasmin Ingram , Oluwasegun Olujide , Nadeem A. Sheikh +4 more | Current Oncology

There is growing evidence relating to the risk of cancer in people with obesity. Obesity is already established as one of the strongest predisposing factors to cancer, and 'obesity-related' cancers … There is growing evidence relating to the risk of cancer in people with obesity. Obesity is already established as one of the strongest predisposing factors to cancer, and 'obesity-related' cancers have been defined in previous studies. In this review article, we examine the epidemiological relationship and describe the potential pathophysiological mechanisms that underpin the association between obesity and cancer. These include hormonal and growth factors that are in abundance in persons living with obesity and thereby increase cancer risk. Additionally, the increased disposition towards chronic inflammation in obesity also confers cancer risk. We also examine the impact of obesity on cancer treatment outcomes, focusing on surgery, chemotherapy, and immunotherapy. Conversely, we underline the impact of weight loss on cancer risk by examining different weight loss strategies.

Understanding Trends in Incidence and Management of Pregnancy‐Associated Breast Cancer in a National Sample Using Claims Data

2025-06-19

Kaamya Varagur , Joseph G. Ribaudo , Matthew Keller +7 more | Journal of Surgical Oncology

ABSTRACT Background and Objectives Breast cancer incidence in young women is increasing globally. Here, we examine trends in incidence, management, and reconstruction for pregnancy‐associated breast cancer (PABC) in women 18–45. … ABSTRACT Background and Objectives Breast cancer incidence in young women is increasing globally. Here, we examine trends in incidence, management, and reconstruction for pregnancy‐associated breast cancer (PABC) in women 18–45. Methods Females aged 18–45 with breast cancer between 2007 and 2021 were identified in the Merative MarketScan Commercial and Multi‐State Medicaid Databases. We analyzed trends in incidence of PABC, treatments, and latency to treatments for PABC versus non‐PABC. Results A total of 1189 patients with PABC and 36 683 with non‐PABC were included. Over the study period, the proportion of breast cancer cases classified as PABC increased (2.36% of cases from 2007 to 2009, to 3.94% from 2019 to 2021; p < 0.001). Patients with PABC experienced higher rates of neoadjuvant chemotherapy, mastectomy, trastuzumab, and ovarian suppression therapy than patients with non‐PABC, and lower rates of adjuvant radiation and breast conserving surgery ( p ≤ 0.001). PABC status did not independently predict increased latency from diagnosis to tumor resection surgery when controlling for receipt of neoadjuvant chemotherapy ( p = 0.154). Patients with PABC experienced comparable rates of delayed or immediate implant and autologous reconstruction as patients with non‐PABC, but experienced increased latency to delayed implant reconstruction ( p < 0.001). Conclusions PABC rates are increasing among women 45 and younger. Patients with PABC experience differences in types of medical/surgical treatments received and timing of post‐mastectomy reconstruction.

Gravida and birth outcomes prior to and after diagnosis of early age onset colorectal cancer among female patients: Population-based epidemiologic studies

2025-06-18

Niki Oveisi , Eric C. Sayre , Sharlene Gill +7 more | Cancer Epidemiology Biomarkers & Prevention

Abstract Background: Early age-onset colorectal cancer (EAO-CRC) strikes during the reproductive years, yet pregnancies before and after diagnosis have not been thoroughly studied. Our objective was to comprehensively examine: 1) … Abstract Background: Early age-onset colorectal cancer (EAO-CRC) strikes during the reproductive years, yet pregnancies before and after diagnosis have not been thoroughly studied. Our objective was to comprehensively examine: 1) the relationship between gravida and EAO-CRC; and 2) the relationship between EAO-CRC and births post cancer diagnosis. Methods: We conducted a case-control and a cohort study using administrative health data from British Columbia, Canada, of females diagnosed with EAO-CRC from 2005 to 2017, and age and sex matched cancer-free controls. Multivariable logistic regression models were used to evaluate: 1) the association between gravida assessed over the 5-year prodrome period before cancer diagnosis and EAO-CRC; and 2) the association between EAO-CRC and births assessed over a 5-year period following cancer diagnosis. Results: The study sample consisted of 865 females (age at EAO-CRC diagnosis 42.5 +/- 6.1 years) with EAO-CRC and 8,291 controls (42.4 +/- 6.3 years). Females with a gravida of ≥2 in the 5-year prodrome period had 1.82 times the odds of EAO-CRC compared to those with gravida of 0 (odds ratio [OR] 1.82; 95% confidence interval (CI) 1.19, 2.78). Post cancer diagnosis, females with EAO-CRC had significantly lower odds of giving birth within five years (OR 0.23; 95% CI 0.15, 0.37). Older age, lower income, rural residence, and greater healthcare utilization were associated with lower odds of post-diagnosis births. Conclusions: Our study highlights the complex relationship between reproductive health and EAO-CRC. Impact: Findings indicate a need for comprehensive psychosocial support addressing family planning for female EAO-CRC patients.

Association Between Levonorgestrel-Releasing Intrauterine System Exposure Duration and Breast Cancer Incidence

2025-06-18

Wei How Lim | Obstetrics and Gynecology

Mammographic calcifications association with risk of advanced breast cancer

2025-06-17

Karla Kerlikowske , Linn Abraham , Brian L. Sprague +4 more | Breast Cancer Research and Treatment

Abstract Purpose Mammographic calcifications on mammograms with a negative/benign assessment are associated with increased breast cancer risk. Associations with advanced breast cancer risk are unknown. We evaluated whether calcifications recorded … Abstract Purpose Mammographic calcifications on mammograms with a negative/benign assessment are associated with increased breast cancer risk. Associations with advanced breast cancer risk are unknown. We evaluated whether calcifications recorded on mammography reports are associated with advanced invasive breast cancer risk. Methods We included 3,710,313 screening mammograms with a negative/benign final assessment performed on 991,991 women aged 40–74 in the Breast Cancer Surveillance Consortium associated with 7229 advanced cancers. We calculated cumulative 5-year advanced (prognostic pathologic stage ≥II) breast cancer risk and hazards ratios (HR) adjusted for clinical risk factors according to presence or absence of calcifications by menopausal status, dense (heterogeneously or extremely dense) vs. non-dense (almost entirely fatty or scattered fibroglandular density) breasts, body mass index (BMI) < 25 kg/m 2 vs. ≥ 25 kg/m 2 . Results Prevalence of calcifications was 6.1% among women who developed advanced breast cancer vs. 3.6% among others. Overall associations of advanced cancer with calcifications were similar for premenopausal (HR = 1.4; 95% CI 1.1–1.9) and postmenopausal (HR = 1.5; 95% CI 1.2–1.7) women. Compared to postmenopausal women with non-dense breasts and BMI < 25 kg/m 2 without calcifications [cumulative 5-year advanced cancer incidence = 1.6 (95% CI 1.3–2.0) per 1000 women], postmenopausal women with dense breasts, BMI ≥ 25 kg/m 2 , and calcifications had 5.5-fold (95% CI 3.9–7.7) higher advanced cancer risk [cumulative 5-year advanced cancer incidence = 10.2; (95% CI 7.0–13.3) per 1000 women]. Results were similar for premenopausal women. Conclusion Mammographic calcifications increase advanced cancer risk beyond having dense breasts and being overweight/obese. Future research should investigate strength of associations by type of calcification and incorporation of calcifications into advanced cancer risk models for improvement in model accuracy.

Diagnostic and Therapeutic Challenges in Pregnancy-Associated Breast Cancer: A Literature Review

2025-06-16

Maria Michalska , Kinga Kowalik , Aleksandra Zielińska +7 more | Quality in Sport

Introduction: Pregnancy-associated breast cancer (PABC) is an increasingly diagnosed malignancy, typically occurring during pregnancy or within one year postpartum. This review summarizes current knowledge on PABC diagnosis, treatment and clinical … Introduction: Pregnancy-associated breast cancer (PABC) is an increasingly diagnosed malignancy, typically occurring during pregnancy or within one year postpartum. This review summarizes current knowledge on PABC diagnosis, treatment and clinical management, with attention to both maternal outcomes and fetal safety. Diagnostic: The diagnosis of PABC requires careful consideration of both maternal health and fetal safety. Diagnostic process typically begins with the detection of a palpable mass, followed by ultrasound imaging and biopsy. Mammography and MRI may be used selectively, whereas CT and PET-CT are avoided due to radiation exposure. Physiological changes during pregnancy often delay recognition. Histopathology: Histopathological evaluation of PABC follows standard classifications, including the AJCC TNM and WHO systems, with assessment of ER, PR, HER2, Ki-67, and tumor grade. The most common histological type is ductal infiltrating adenocarcinoma. Treatment: Treatment of PABC is complex and multifactorial, often requiring adjustments to standard protocols to balance effective maternal therapy with fetal safety. Surgery is considered safe during all trimesters, while chemotherapy is typically used in the second and third trimesters. Trastuzumab, tamoxifen, and radiotherapy are generally avoided due to fetal risks, though radiotherapy may be considered in selected cases after thorough evaluation. Conclusion: Pregnancy-associated breast cancer requires an individualized, multidisciplinary approach, with diagnosis and treatment tailored to balance effective maternal care and fetal safety.

Inflammatory Burden Index and Cancer Prevalence: Insights from a Nationally Representative Study on the Predictive Role of Systemic Inflammation

2025-06-16

Mengmeng Wang , Zihan Li , Xin-Jing Cui +1 more | Research Square (Research Square)

<title>Abstract</title> Background Cancer remains a major global health burden with persistently high incidence and mortality rates. Chronic systemic inflammation plays a pivotal role in tumor initiation and progression. The Inflammatory … <title>Abstract</title> Background Cancer remains a major global health burden with persistently high incidence and mortality rates. Chronic systemic inflammation plays a pivotal role in tumor initiation and progression. The Inflammatory Burden Index (IBI), a composite biomarker derived from routine blood parameters, has shown promise in cancer prognosis. However, evidence from large-scale, population-based studies on its association with cancer prevalence is scarce. Objective To investigate the association between IBI levels and cancer prevalence in a representative U.S. population, providing insights into the role of systemic inflammation in cancer risk stratification. Methods Data from 10,196 participants of the National Health and Nutrition Examination Survey (NHANES) 2005–2020 were analyzed. Cancer prevalence was based on self-reported diagnoses, and IBI was calculated using established formulas. Multivariable logistic regression and restricted cubic spline (RCS) analyses were employed to evaluate the relationship between IBI levels and overall and site-specific cancer prevalence. Results Higher IBI levels were significantly associated with increased cancer prevalence (9.92%). Adjusted logistic models confirmed a positive relationship between IBI and cancer risk (OR: 1.37, 95% CI: 1.04–1.80; P = 0.02). Notably, stronger associations were observed for breast (OR: 1.99) and prostate cancer (OR: 2.02). Subgroup analysis revealed significant interactions between IBI and body mass index (BMI), with amplified risk among individuals with BMI ≥ 25. Conclusions Elevated IBI levels are independently associated with higher cancer prevalence, particularly for breast and prostate cancers. These findings support the utility of IBI as a non-invasive, cost-effective marker for cancer risk stratification in clinical and public health settings.

“A Teachable Moment”—The Prevalence of Overweight and Obesity Among Chinese Colorectal Cancer Survivors and Their Perspectives in the Context of Chinese Culture: A Mixed Method Study

2025-06-16

Zhuyue Li , Kaihan Yang , Hong Chen +3 more | Journal of Transcultural Nursing

Introduction: The study aimed to investigate the prevalence of overweight and obesity among Chinese colorectal cancer survivors, and how they gain weight during treatment. Methods: A sequential mixed method study … Introduction: The study aimed to investigate the prevalence of overweight and obesity among Chinese colorectal cancer survivors, and how they gain weight during treatment. Methods: A sequential mixed method study was conducted. Pearson correlation analysis, univariate analysis and a multivariable-adjusted binary Logistic regression model were constructed to explore risk factors. Semi-structured in-depth interviews were conducted, and content analysis was employed for qualitative data analysis. Results: There were 30.8% overweight and 4.2% obese colorectal cancer survivors. Gender ( b = −1.10), caregiver ( b = −0.76), dietary knowledge ( b = −0.13, anxiety ( b = 0.14), depression ( b = −0.15), duration of illness ( b = 0.95), and tumor staging ( b = −1.25) were significantly associated with overweight and obesity. A total of four categories, six themes, and 12 codes were identified, revealing a “teachable moment” for lifestyle modification. Discussion: One-third of the patients were overweight and obese. Being diagnosed was a “teachable moment” for lifestyle modification, but survivors showed limited knowledge and incorrect weight management goal.

Abstract P5-02-17: Concordance Analysis of Non-Invasive determination techniques of PIK3CA and ESR1 mutations in patients with advanced luminal breast cancer. Study CANIPE

2025-06-13

Teresa Curiel , Carmela Rodríguez , Aurora Casanova +7 more | Clinical Cancer Research

Abstract Approximatly 70% of breast cancer (BC) patients are Hormone Receptors (HR) positive, the most common subtype with the best prognosis. The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with … Abstract Approximatly 70% of breast cancer (BC) patients are Hormone Receptors (HR) positive, the most common subtype with the best prognosis. The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with Endocrine Therapy (ET) is tje standard firs-line therapy for HR+/HER2- metastatic BC. However, 20% of patients are intrinsically resistant, and those who initially respond often develop acquired resistance, making the management of resistant HR+/HER2- metastatic BC a significant clinical challenge. Clinical guidelines emphasize the need of comprehensive real-time monitoring of the dynamic mutational landscape during and after treatment to improve resistance prediction. Early detection of mutations in ESR1 and the PIK3 pathway usinf circulating tumor DNA (ctDNA) may allow the ending of ineffective endocrine therapies and initiation of alternative treatments for these patients, without performing tissue biopsies before radiological progression occurs. To achieve this, it is crucial to implement non-onvasive genotyping that allows better-adapted pharmacologiical interventions. However, clinical trials have been predominantly carried out with selected populations and single drugs (Palbociclib, Ribociclib or Abemaciclib). There is a lack of studies of optimal agreemnt between diagnostic methods, especially in liquid biopsy. There is no relieble data abaout PIK3CA or ESR1 status in ctDNA from real-world cohorts that could help to define the best testing strategy for the clinica routine. Therefore, it is imperative to establish evidence that the use of ddPCR is equally or more sensitive for ctDNA analysis than qPCR or NGS, the current gold standard methods. Aim: This study aims to perform a concordance analysis between NGS and ddPCR technologies for detecting mutations in PIK3CA and ESR1 by testing the ctDNA from HR+/HER2- metastatic breast cancer patients. M&M: CANIPE is a randomised, open-label study performed al 14 Spanish hospitals in 6 autonomous communities. Patients aged 18 years or older, with confirmed HR+/HER2- breast cancer, stage IV, Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 to 2, who iniciate first-line tratment with CDK4/6i plus aromatase inhibitors. All procedures followed the Helsinki Declaration guidelines and were approved by the Ethics Commitee of Santiago-Lugo under approval reference number 2022/386. All patients provide written informed consent. A total of 60 women were recruited at baseline (before therapy initiation) while 21 patients at 10 months after treatment. 40 mL of blood was obteined from each patient at both time points. For ddPCR, cfDNA was isolated from 5 mL of plasma using the QIAamp Circulating Nucleic Acid Kit (Qiagen, Venlo, The Netherlands). Multiplex ddPCR was performed with de Bio-Rad QX-200 system to identify PIK3CA mutations, including the most frequent variants (E542K, E545K, H1047L, H1047R, R88Q, N345K, C420R, E545A, E545G,Q546K), and ESR1 mutations (L536R, D538G, E380Q, Y537C, /537S, Y537N,S463P). A mutation was considered present if at least 6 mutated events were detected by ddPCR. Additionally, for NGS, cfDNA was isolated from 4 mL of plasma and analysed with the AVENIO ctDNA Expanded kit (Roche Diagnostics), which includes 77 genes, including PIK3CA and ESR1. An allele fraction od 0.5 % or higher was consideredindicative of a mutation. Results: At baseline, and considering the pre-defined criteria, ctDNA analysis detected PIK3CA mutations in 32.25% and 44.44% of patients by AVENIO and ddPCR, respectively. ESR1 mutations were detected in 3.22% and 9.37% by AVENIO and ddPCR, respectively. For PIK3CA mutations, the Kappa value was 0.62 (p-value: 0.0004) and 0.47 for ESR1 mutations (p-value: 0.0039). However, when NGS data was included for mutations with allele fraction less than 0.5%, the Kappa value was 0.92 for PIK3CA and 1 for ESR1, indicating almost perfect agreement bvetween the two technologies (p-value &lt; 0.0001). Conclusion: The analysis of ctDNA bu Multiplex ddPCR of HR+/HER2- metastatic breas cancer patients represent a sensitive tool to identify PIK3CA and ESR1 mutations with a high concordance compared with the NGS, which is currently the reference technology. Citation Format: Teresa Curiel, Carmela Rodriguez, Aitor Rodriguez Casanova, Nerea González, Ramón Lago-Lestón, Martín Giráldez, Alicia Abalo, Carmen Abuín, Maribel Aibar, Patricia Palacios, Juan Cueva, Marta carmona, Alexia Cortegoso, Serafín Morales, Josep Gumá, Mariana López Flores, Yolanda Fernández, Isaura Fernádez, Ignacio Fernández, María Gión, Carolina Pena, Jesús García Mata, Andrea Saenz de Miera, Angel Díaz Lagares, Laura Muinelo Romay, Clotilde Costa, Rafael López López. Concordance Analysis of Non-Invasive determination techniques of PIK3CA and ESR1 mutations in patients with advanced luminal breast cancer. Study CANIPE [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-02-17.

Abstract P4-06-26: Fertility Preservation in Young Women with Breast Cancer in Brazil: Patient Profiles and Challenges in a Real World Scenario

2025-06-13

Caroline Cançado Avelar , Rui Cerqueira , José Tadeu Campos de Avelar +7 more | Clinical Cancer Research

Abstract Introduction: Breast cancer, whose incidence among adolescents and young adults (AYA) has increased in recent years, harbors many global challenges and unmet needs. Among them, concerns regarding fertility preservation … Abstract Introduction: Breast cancer, whose incidence among adolescents and young adults (AYA) has increased in recent years, harbors many global challenges and unmet needs. Among them, concerns regarding fertility preservation stand out. Many barriers, such as financial support, lack of timely referral and availability of cryopreservation have been identified, which may be exacerbated in developing countries. In this study, we accessed real-world data regarding fertility preservation in Brazil among AYA breast cancer patients. Methods: This retrospective cross-sectional observational study was conducted in a private referral network cancer center in Brazil. Breast cancer premenopausal patients aged 15 to 39 years undergoing systemic treatment between 2019 and 2023 were identified. Clinical data was obtained retrospectively from medical records. We searched for demographic and clinicopathologic characteristics and data regarding fertility counseling, funding and the practices of fertility preservation groups, aiming to map out the care among this population. Descriptive statistics were used to summarize data. Results: In this cohort, 60 AYA breast cancer patients were identified, representing 10.9% of the disease diagnosis. Of them, 49 (81.6%) underwent chemotherapy, most with anthracycline-containing regimens (82.0%). However, only 23 (38.3%) of the patients had fertility counseling documented in their medical records. Among these referred patients, 12 (52.1%), in fact, proceeded to evaluation by the reproductive medicine team. Oocyte collection for cryopreservation was performed in 7 patients, representing 14.2% under systemic treatment. When this technique was not feasible, some patients (n=3) received LHRH agonists in monotherapy, considered a less effective method. The average time between diagnosis and the initiation of oncologic treatment was also analyzed. Among patients who underwent fertility counseling, it was 25 days (range, 7-34), a similar timeframe to those who did not (19 days, range 3-37). Considering only the patients who underwent oocyte collection, the median time was 26 days (range, 9-34). Regarding fertility preservation funding, procedures and medical expenses were not covered or reimbursed by health insurance but solely by the patient. Conclusion: The present study shows a low rate of cryopreservation among AYA breast cancer patients who underwent systemic treatment in Brazil, although this procedure did not lead to clinically relevant delays in the initiation of chemotherapy. Potential barriers include a poor rate of fertility counseling and funding concerns. Given Brazilian economic and sociodemographic inequalities, this scenario may be even worse in the public setting and outside referral centers. This study highlights the need for standardized protocols to ensure that all AYA patients are counseled on fertility preservation from initial diagnosis. This includes integrating multidisciplinary teams, providing specific training for oncologists and other healthcare professionals and establishing automatic referrals for consultation with fertility specialists. Additionally, providing psychological support is crucial to help patients make informed decisions aligned with their future maternity desires. Thus, further studies would support national cancer care improvements among this population. Citation Format: Caroline Avelar, Renata Arruda Cerqueira, José Tadeu Campos de Avelar, Enaldo Melo de Lima, Rivia Mara Lamaita, João Pedro Costa Apolinário, Ianca Elirrayeth Rocha Mendes, Luísa Lazarino de Souza Campos, Neila Caroline Alves Amaral, Catharina Cançado Avelar, Paulo Henrique Costa Diniz. Fertility Preservation in Young Women with Breast Cancer in Brazil: Patient Profiles and Challenges in a Real World Scenario [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-06-26.

Abstract PS16-02: Polygenic risk score as an aid for risk stratification in benign breast disease

2025-06-13

Kush R. Lohani , Stacey J. Winham , Bryan M. McCauley +7 more | Clinical Cancer Research

Abstract Background: Pathologic diagnoses of benign breast disease (BBD), subclassified by histologic impression as non-proliferative disease (NP), proliferative disease without atypia (PDWA) and atypical hyperplasia (AH), predict increasing breast cancer … Abstract Background: Pathologic diagnoses of benign breast disease (BBD), subclassified by histologic impression as non-proliferative disease (NP), proliferative disease without atypia (PDWA) and atypical hyperplasia (AH), predict increasing breast cancer risk (BC) in populations; however improved methods to predict individual risk are needed. Research has established that a polygenic risk score (PRS) based on variation in 313 single nucleotide polymorphisms (SNPs) predicts breast cancer (BC) risk in the general population, but data among women with BBD are limited. Thus, we evaluated a PRS in a large single institutional study to assess associations with BBD subtype and BC risk. Methods: With IRB approval, we evaluated 3,943 subjects in our institutional BBD cohort with existing genotyping data or germline buccal DNA that was genotyped with Illumina’s Global Screening Array; these comprised a sample from the underlying BBD cohort of 20,380 women from years 1967-2013, for whom followup data were available on later BC events. PRS was computed using 261 of the published 313-PRS SNPs that were commonly available across all datasets. The PRS was a weighted linear combination of the genotypes and odds ratios from the largest BC genome-wide association study (GWAS) to date. PRS was standardized within genotyping platform and evaluated per one standard deviation. BBD histologic impression was based on pathology review as NP, PDWA, or AH. Odds ratios (OR) and 95% confidence intervals (CI) for the PRS and histologic impression were calculated using logistic regression, adjusted for age and genotyping platform. Models were examined for histologic impression alone, PRS alone, and the two factors combined. Also, associations between PRS and histologic impression were assessed as well as potential interactions between the two variables on BC risk. Results: Of the 3,943 women with BBD and PRS data, 857 were cases (i.e., developed BC after BBD) and 3086 were controls. Across the entire sample, histologic impression was NP in 56%, PDWA in 35%, and AH in 9%. The PRS scores after normalizing by platform across the 3,943 women in the sample had a mean of -0.007 with a standard deviation of 1.001 and a range of -3.67 to 3.94. In multivariable models estimating risk of BC based on a referent of NP and mean PRS, factors associated with risk included: PRS (per-SD OR=1.52, 95% CI: 1.39-1.66); PDWA (OR=1.63, 95%CI: 1.35-1.97) and AH (OR=1.71, 95%CI: 1.26-2.30), all significant at P&lt;0.001. An interaction term between BBD histologic impression and PRS was not statistically significant (p&gt;0.70). Conclusions: Our analysis suggests that both BBD histologic subtype and PRS are independently associated with BC risk; thus, PRS information may be helpful for personalizing risk assessment in the setting of BBD. Citation Format: Kush R Lohani, Stacey J Winham, Bryan McCauley, Robert A Vierkant, Tanya L Hoskin, Matt Jensen, Jessica Fischer, Denice Gehling, Christine Schmelzer, Lori Denison, Laura Pacheco-Spann, Lisa Seymour, Derek C Radisky, Mark E Sherman, Celine M Vachon, Amy C Degnim. Polygenic risk score as an aid for risk stratification in benign breast disease [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS16-02.

Abstract P4-11-09: Epigenetic Alterations Affecting Cell Morphogenesis and Tumor Plasticity Pathways in Primary Tumors of Breast Cancer Patients with High Nodal Involvement

2025-06-13

Sookyung Ahn , Andrés F. Bedoya-López , Miquel Ensenyat-Méndez +3 more | Clinical Cancer Research

Abstract Introduction: Survival rates for patients with breast cancer have improved significantly with widespread screening and effective systemic therapies. However, patients who present with advanced nodal stage at diagnosis have … Abstract Introduction: Survival rates for patients with breast cancer have improved significantly with widespread screening and effective systemic therapies. However, patients who present with advanced nodal stage at diagnosis have higher rates of distant relapse and require more aggressive therapies than patients with pathologic N1 disease (pN1). Understanding the molecular alterations that occur in primary breast cancer (BC) that drive progression to a higher nodal stage (&gt;pN1) could uncover potential therapeutic targets for patients with regionally metastatic BC. Given that epigenetic mechanisms represent that crucial layer of dynamic change that regulates genome-wide gene expression, we assessed the DNA methylation profiles of primary BC at various nodal stages. Methods: We conducted an exploratory study using a well-annotated, retrospective cohort of ER+/HER2- treatment-naive primary BC from patients with clinically positive nodes and complete pathologic nodal data treated at Duke University (n=49, 30 cases pN1 vs. 19 cases &gt;pN1). DNA was extracted from paraffin-embedded samples, and DNA methylation profiling was performed using the Illumina EPIC BeadChip v1 arrays. The ChAMP package was utilized to correct batch effect, and the Wilcoxon test was used to identify Differentially Methylated Sites (DMS). Tumor content purity was assessed using the LUMP algorithm and Gene Ontology enrichment of the DMSs was examined with the GOmeth tool. Data analysis and visualization were performed using the R packages ggplot2 (v. 3.4.4), circlize (v. 0.4.16), and gplots (v. 3.1.3.1), with data management facilitated by the tidyverse (v. 2.0.0) collection. Results: Tumor purity was similar between the two groups (p&gt;0.05). The comparison revealed distinct DNA methylation patterns in 962 genomic regions between pN1 and &gt;pN1 tumors (differential methylation &gt; 15%, p&lt;0.01); 683 regions were hypermethylated and 279 were hypomethylated in the &gt;pN1 group. There was a significant enrichment of biological processes associated with morphogenesis among the hypermethylated sites, with 22 of the 43 affected molecular pathways linked to cellular morphogenesis. Additionally, epigenetic alterations were predominantly found in pathways related to the response to bone morphogenic protein (BMP). Expression-methylation Quantitative Trait Loci (emQTLs) were linked to epithelial to mesenchymal transition (EMT) genes in &gt;pN1 tumors. Finally, higher methylation of the protocadherin cluster genes (PCDHGA) and regions encompassing DUSP6 and KRT7 genes were identified in tumors of higher nodal stage. These findings suggest inherent or acquired epigenetic alterations in primary BC associated with higher nodal stage. Conclusions: Understanding the mechanisms underlying lymph node invasion in breast cancer progression is crucial for improving the clinical management of patients with BC. This study indicates that ER+/HER2- primary tumors from patients with higher nodal involvement have an epigenetic predisposition to activate morphogenic differentiation and EMT more efficiently than patients with lower nodal involvement. Deeper insight into these alterations could contribute to more accurate prognostic tools, the development of novel therapeutic approaches, and potentially help avoid more aggressive axillary procedures. Citation Format: Sookyung Ahn, Andrés F. Bedoya-López, Miquel Ensenyat-Mendez, Pere Llinàs-Arias, Diego M. Marzese, Maggie L. DiNome. Epigenetic Alterations Affecting Cell Morphogenesis and Tumor Plasticity Pathways in Primary Tumors of Breast Cancer Patients with High Nodal Involvement [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-11-09.

Abstract P1-07-05: Association of BMI variations with response to neoadjuvant chemoimmunotherapy for early-stage triple-negative breast cancer

2025-06-13

Bethania Santos | Clinical Cancer Research

Abstract Introduction: Increased body mass index (BMI) has been associated with improved response to immune checkpoint inhibitors (ICIs) in multiple cancer types. This phenomenon has been attributed in part to … Abstract Introduction: Increased body mass index (BMI) has been associated with improved response to immune checkpoint inhibitors (ICIs) in multiple cancer types. This phenomenon has been attributed in part to obesity, higher adipose tissue composition in the breast and/or metabolic syndrome leading to T-cell dysfunction. However, BMI may vary during neoadjuvant therapy due to dietary changes, toxicity of therapy or psychosocial factors including anxiety and stress. This study aims to investigate the impact of BMI variation on pathological complete response (pCR) for patients with early-stage triple negative breast cancer (TNBC) receiving neoadjuvant chemotherapy with immunotherapy. Methods: Patients with early-stage TNBC diagnosed between July 1, 2021, and December 31, 2023, were identified through two institutional databases. All patients received the KEYNOTE-522 regimen. Based on their baseline BMI, patients were categorized as obese (BMI ≥30) or non-obese (BMI &lt;30). The chi-square test of independence was used to assess whether a significant association exists between BMI variation categories, greater than 1 point vs. 1 point or less (7lb/3Kg) and pCR status (achieved vs. not achieved). Univariate and multivariate analyses were performed using logistic regression to identify factors associated with pCR. Results: Among the 264 patients identified, the median age was 52.9 years, the average BMI was 28.3, and 119 (45.1%) were obese. In univariate analysis, a BMI of ≥30 at baseline was associated with an improved rate of pCR (p &lt; 0.1). In multivariate analysis, patients with a BMI ≥30 had improved pCR rates [OR (95% CI): 1.85 (1.08, 3.20), p &lt; 0.05]. An unbiased selection of 38 patients from our cohort was analyzed to determine if BMI variation between the beginning and end of neoadjuvant treatment impacts outcomes. Among patients with a BMI variation &gt; 1 point, 78.95% (15 out of 19) achieved a pCR, while among patients with a BMI variation &lt; 1, only 21.05% (4 out of 19) achieved a pCR. A chi-square test of independence indicated a statistically significant difference between the two groups (χ2 = 12.9240, p = 0.002). Conclusion: These findings highlight the importance of considering BMI variation as a factor in treatment outcomes. Nutritional status, changes in diet and physical activity during treatment can influence BMI variation. Intrinsic differences in tumor biology might influence both BMI variation and response to treatment. More aggressive tumors might cause more weight loss, which could be linked to the high activity of the immune response. Further understanding these factors should help to interpret the results and improve treatment outcomes. Larger, prospective studies are needed to confirm these results. Citation Format: Bethania Santos. Association of BMI variations with response to neoadjuvant chemoimmunotherapy for early-stage triple-negative breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-07-05.

Abstract P4-02-22: Temporal Changes in Breast Cancer Reproductive Risk Factors Among Women in Southwest Nigeria: Data from The Nigerian Breast Cancer Survey

2025-06-13

Gideon T Dosunmu , Olasubomi J. Omoleye , Mihai Giurcanu +2 more | Clinical Cancer Research

Abstract Background: The incidence of breast cancer in Sub-Saharan Africa (SSA) has surged by 247% from 1990 to 2019, with a notable prevalence among women under 50 years of age. … Abstract Background: The incidence of breast cancer in Sub-Saharan Africa (SSA) has surged by 247% from 1990 to 2019, with a notable prevalence among women under 50 years of age. The understanding of evolving risk factors has however remained heavily reliant on data and guidelines extrapolated from High Income Countries (HIC), which may not accurately reflect the unique epidemiological profiles in Nigeria and other Low to Middle Income Countries (LMIC) in SSA. Given the stark mortality rates amidst rising incidence, our study aims to refine the understanding of the trend of breast cancer risk factors in low-income countries using the Nigerian Breast Cancer Study (NBCS) data.Methods: This is a retrospective study using the NBCS database consisting of 2314 healthy Nigerian women aged 18 and older enrolled between 1998 to 2017. Participants were grouped into six birth cohorts: &lt;1940, 1940-49, 1950-59, 1960-69, 1970-79, and ≥1980. The primary dependent variables were age at menarche, thelarche, number of pregnancies, parity, and duration of breastfeeding. Descriptive statistics was employed to assess reproductive characteristics, while univariate regression models explored the relationship between reproductive risk factors and birth decade. Trend analyses were conducted to identify significant changes across the cohorts. Results: The average age at menarche decreased from 16.1 years in women born before 1940 to 15.1 years in those born after 1980 (p &lt; 0.001). The mean age at thelarche was centered around 13 years across cohorts. However, regression analysis indicated a slightly increasing trend in thelarche age over time (coefficient = 0.090, p = 0.001), with decade of birth explaining a very small portion of the variability (R-squared = 0.0048). This slightly increasing trend in thelarche age is not consistent with the sharp decreasing trend in menarche age. This discrepancy is difficult to explain physiologically and warrants further investigation. The number of pregnancies per woman similarly declined, from an average of 7 in the pre-1940 cohort to 4 in the post-1980 cohort (p &lt; 0.001). Parity trends mirrored this decline, with a significant reduction over time (p &lt; 0.001). The mean age at first live birth remained consistent at approximately 23 years across cohorts. The mean duration of breastfeeding per child also decreased from 18.3 months for those born before 1940 to 14.8 months for those born after 1980 (p &lt; 0.001). Conclusion: Our study provides important insights into the temporal changes in reproductive health risk factors among Nigerian women across various birth cohorts. Although some of our findings indicate shifts that might parallel trends observed in HIC, it is important to highlight notable differences such as events like thelarche and menarche which occur approximately 2 to 3 years later in the Nigerian population compared to their counterparts in HIC. There are also discernible differences in breastfeeding duration and parity trends. Future studies will evaluate the role of genomic and environmental risk factors in the etiology of breast cancer in Nigerian women. This study underscores the need for population-specific risk assessment tools to accelerate progress in breast cancer prevention in LMICs. Citation Format: Gideon Dosunmu, Olasubomi Omoleye, Mihai Giurcanu, Dezheng Huo, Olufunmilayo I. Olopade. Temporal Changes in Breast Cancer Reproductive Risk Factors Among Women in Southwest Nigeria: Data from The Nigerian Breast Cancer Survey [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-02-22.

Abstract P3-03-13: Ethnic and Geographic Disparities in Mucinous Breast Cancer

2025-06-13

In-Ae Park , Young Jin Heo , Sung Jae Park | Clinical Cancer Research

Abstract Introduction: Mucinous breast cancer (MBC) is a rare subtype of invasive breast cancer which accounts for one to four percent of overall invasive breast cancer in the United States. … Abstract Introduction: Mucinous breast cancer (MBC) is a rare subtype of invasive breast cancer which accounts for one to four percent of overall invasive breast cancer in the United States. The clinical features of MBC have not been fully understood due to limited patient data. Here, we report ethnic and geographic disparities in patients with MBC. Method: Mortality and overall survival rates (OS) were obtained from the Surveillance, Epidemiology, and End Results (SEER) Stat Database 17-registry (2000-2021). The 7th edition of American Joint Committee on Cancer (AJCC) staging was used due to the unavailability of differentiation grade data in the 8th edition of AJCC staging. Patient subgroups were divided into ethnicity (White, Black, Asian American and Pacific islanders; AAPI), household income (&gt;=$75,000 vs &lt;$75,000 per year), age of diagnosis (25-45 vs 45-65 vs 65+ years), and geographics (metropolitan vs nonmetropolitan area). Propensity score matching (PSM) was used to reduce the effect of confounding factors such as surgery, chemotherapy, radiation therapy, stage, grade, hormone receptor status (estrogen receptor; ER and progesterone receptor; PR), and human epidermal growth factor receptor 2 (HER2) status. Univariate and multivariate Cox regression analyses were used to obtain independent prognostic factors. Patients with duplicate record, missing information regarding confounding factors were excluded in the analysis. Result: Overall, 5,219 patients were included in the final analysis. The independent prognostic factors were age of diagnosis, race, stage, differentiation grade, hormone receptor status (ER and PR), HER2 status, metastases (bone, brain, liver, and lung), surgery, chemotherapy, radiation, income, and marital status. In ethnic subgroups, AAPI showed better OS than in White before and after PSM (before PSM, HR 0.50, 95% CI, 0.41-0.62, p&lt;0.01; after PSM, HR 0.54, 95% CI, 0.42-0.69, p&lt;0.01). White and Black patients did not reveal significant differences in survival. (HR 1.03, 95% CI, 0.88-1.21, p=0.74). After PSM, White patients had an OS benefit than in Black (HR 0.56, 95% CI, 0.44-0.71, p &lt;0.01). In geographic subgroups, patients in the metropolitan areas did not show significant difference compared to patients in the nonmetropolitan areas before PSM (HR 0.87, 95% CI, 0.74-1.02, p=0.09). However, patients in the metropolitan areas exhibited better OS compared to patients in nonmetropolitan areas (HR 0.61, 95% CI, 0.48-0.77, p&lt;0.01) after PSM. In income subgroups, patients with household income &gt;=$75,000 revealed better OS than those who have income less than $75,000 before PSM (HR 0.82, 95% CI, 0.74-0.91, p&lt;0.01). However, those groups did not show statistical significance in OS after PSM (HR 0.89, 95% CI, 0.80-1.00, p=0&lt;0.01). Conclusion: Overall, mortality and OS varied among different ethnic groups and regions, though additional studies are warranted for Native Americans or Alaskans with a larger patient dataset. In regards to primary prevention, an early intervention could be especially beneficial for patients in rural areas while MBC is known for its good prognosis. Furthermore, several possible confounding factors such as alcohol or smoking could be further controlled if they are included in the SEER dataset in the future. In addition, the use of AJCC 8th edition with differentiation grade data is warranted in the future. Citation Format: Inae Park, Yu Jung Heo, Sungjae Park. Ethnic and Geographic Disparities in Mucinous Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-03-13.

A Mathematical Model for the Effect of Obesity on Cancer Growth Under the Treatment of Chemotherapy

2025-06-13

Winnie Fernando , G. V. R. K. Vithanage , A. Dissanayake +3 more | MOLECULAR SCIENCES AND APPLICATIONS

Obesity is a burning health problem in the modern world. Bad food habits, lack of exercises, genetics and for some other reasons caused to weight gain in human body. Obesity … Obesity is a burning health problem in the modern world. Bad food habits, lack of exercises, genetics and for some other reasons caused to weight gain in human body. Obesity causes to so many health diseases among them cancer is a prominent disease. Mainly we need to study how obesity effects on a cancer. In this research we modified a mathematical model by using Nonlinear Ordinary Differential Equations. We found equilibrium points of the subsystem and there we calculate threshold levels for the Bistability patterns how we can cure cancer completely or control the disease. After studying the subsystem, we considered the equilibrium points of the full system. By using some real valued data, we conduct a Numerical Analysis for the constructed model. Then we conduct a Stability Analysis and there we study what are the most affecting equilibriums for controlling tumor for treatments. Inverse carrying capacity of fat plays a critical role in controlling cancer. Then we conduct a Bifurcation analysis for inverse carrying capacity of fat and study how tumour level fluctuates. There we observed some important results, that is when fat level decreases, we can remove cancer completely and higher fat levels can hinder the chemotherapy drugs. These results are very important in Biomedical Engineering.

Abstract P5-06-08: Molecular features of Pregnancy Associated Breast Cancer from a tertiary care cancer centre in India

2025-06-13

Jyoti Bajpai , Rohan Chaubal , Rajiv Sarin +7 more | Clinical Cancer Research

Abstract Background: Pregnancy-associated breast cancer (PABC) encompassing breast cancer diagnosed during pregnancy or one-year post-partum is a rare and challenging entity wherein oncologists need to safeguard maternal oncological and foetal … Abstract Background: Pregnancy-associated breast cancer (PABC) encompassing breast cancer diagnosed during pregnancy or one-year post-partum is a rare and challenging entity wherein oncologists need to safeguard maternal oncological and foetal outcomes simultaneously. Little is known about genomic signatures which is worth exploring to throw light on aetiopathogeneses, prognosticators and might reveal potential targets with therapeutic relevance. Aim: The study aimed to identify the molecular signatures to identify potential pathways implicated in pathogenesis and therapeutically relevant targets and independent prognosticators for PABC. Methods: Patients with histologically confirmed breast cancer who were pregnant or diagnosed within one year of last pregnancy were included in study during the year 2013-2020 at our tertiary care cancer centre. Bio-specimens (tumour, tumour-adjacent normal, whole blood or plasma) were collected from the patients and the samples were subjected to DNA and RNA extraction and library preparations and then were sequenced at 200 X for tumour and 100 X for blood/tumour adjacent normal on an Illumina Platform and after through check for the quality control were analysed. Results: There was a total of 104 patients enrolled in the registry from the year 2013-2020.Of these, 55 patients contributed at least one bio-specimen (tumour, tumour-adjacent normal, whole blood or plasma) to this study. Among those,7/55 samples were paired (Tumour and blood), with 9 were only plasma. Of the remaining 48 patients, 7 had paired (tumour and normal) samples, 38 had tumours alone and 3 had germlines alone (2 whole blood, one tumour adjacent normal). All the samples were subjected to DNA and RNA extraction.40/48 patients had at least one analyte (DNA or RNA) available. DNA from 29/38 tumour alone, and 6/7 with paired samples and 2/3 patients with germline alone were subjected to successful library preparation and sequencing at 200 X for tumour and 100 X for blood/tumour adjacent normal on an Illumina Platform. DNA Library prep for 1 patient tumour was unsuccessful due to low DNA quantity; however, that for the total RNA succeeded. RNA from 8 patient tumour samples that passed quality control (RIN&gt;5.0) were also subjected to a total RNA library prep specific for fragmented RNA, followed by sequencing on an Illumina Platform to generate at least 50 million PE reads (100 million total reads). There was an overlap of 7 patients with both WES and RNA-Seq data for tumour samples. Eight out of 38 patients were HER2 positive, with four being ER and/or PR positive and four being ER and/or PR negative. Eleven out of 38 patients were ER and/or PR positive and HER2 negative. Fifteen out of 38 patients were triple negative for ER, PR, and HER2 expression. Four patients were HER2 equivocal; among them, three were ER and PR positive, and one was ER and PR negative. The median age of patients was 30 years (22-45). 32 patients were postpartum at diagnosis while 6 were antepartum at diagnosis. Six patients were node-negative, while 32 were node-positive at diagnosis. Twelve patients presented with de novo metastatic disease at diagnosis, and 19 patients experienced metastatic progression post-diagnosis. The median coverage for WES of Tumour samples was 182X and that for germline samples was 96X. Mutations were identified in PI3KCA (17%), TP53 (4%), and 2% in both. 6 patients harboured germline BRCA mutations. Additional mutations were identified in epigenetic modifiers. Pathways involved in PI3K signalling, mTOR signalling, ECM matrix related signalling and cell cycle related processes were de-regulated. Conclusion: The molecular profiling report for pregnancy-associated breast cancer patients presented here constitutes an invaluable, ultra-rare dataset. This will help in identifying factors associated with etiopathological and prognostic significance as well as relevant potential therapeutic targets for novel targeted therapeutics. This may contribute towards finding novel avenues which may enhance treatment armamentrium in this extremely challenging situation -an unmet need! Citation Format: Jyoti Bajpai, Rohan Chaubal, Rajiv Sarin, Venkatesh Kapu, Khushi Patel, Ankita Singh, Jaya Chitra, Shwetali Pandey, Mrudula Madhav, Aishwarya Raja, Anushree Kadam, Khusboo Gandhi, Altaf Siddiqui, Yogesh Khembhavi, Sushmita Rath, Rajendra Badwe, Sudeep Gupta. Molecular features of Pregnancy Associated Breast Cancer from a tertiary care cancer centre in India [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-06-08.

Abstract P5-04-17: Association Between Ki-67, Body Mass Index, and Stromal Tumor-Infiltrating Lymphocytes in Hormone Receptor-Positive, HER2-Negative Breast Cancer Patients

2025-06-13

Tanmayi Pai , Ramatoulaye Ly , Yaohua Ma +2 more | Clinical Cancer Research

Abstract Background: Stromal tumor-infiltrating lymphocytes (sTILs) and the tumor microenvironment are a growing research focus in breast cancer. Previous studies established the prognostic role of sTILs in triple-negative and human … Abstract Background: Stromal tumor-infiltrating lymphocytes (sTILs) and the tumor microenvironment are a growing research focus in breast cancer. Previous studies established the prognostic role of sTILs in triple-negative and human epidermal growth factor receptor 2 (HER2)-positive tumors, but the role of sTILs remains unclear in hormone receptor-positive (HR+) tumors. A preclinical study demonstrated that obesity exacerbates immune aging, with diet-induced obese mice showing higher frequency of CD8+ TILs, higher PD-1 expression, and decreased Ki-67; donor cells from healthy obese human patients also showed higher PD-1 expression and lower proliferation rate [1]. Hypothesizing that similar patterns might be seen in patients with HR+ HER2-negative breast cancer, we assessed for associations between Ki-67, body mass index (BMI), and sTILs in a cohort of these patients who did not receive neoadjuvant systemic therapy. Methods: We performed a retrospective review of patients with HR+ HER2-negative breast cancer who underwent upfront surgery at Mayo Clinic in Jacksonville, Florida, between January 1, 2022, and June 1, 2023. Height and weight were obtained from the initial breast oncology or breast surgery visit note in the medical record. BMI was calculated using the standardized National Institutes of Health calculator [2]. BMI was categorized as normal (BMI &lt;25), overweight (25 ≤ BMI &lt;30), or obese (BMI 30). sTILs and Ki-67 were evaluated by a breast pathologist. Continuous variables were summarized with the median and interquartile range. Pearson correlation coefficient was estimated to assess for an association between Ki-67, sTILs, and BMI. Wilcoxon rank sum test was performed to identify significant differences of Ki-67 or sTILs between BMI categories. All statistical tests were two-sided, and p-values &lt;0.05 were considered statistically significant. Statistical analysis was performed using R Statistical Software (version 4.2.2; R Foundation for Statistical Computing, Vienna, Austria). Results: A total of 176 patients were included in the analysis. A moderate correlation was seen between Ki-67 and sTILs percentage (%) with Pearson correlation coefficient of 0.37 (95% CI 0.21-0.52, p &lt;0.001), but there was no significant correlation seen between BMI and sTILs % (r = -0.05, 95% CI -0.2-0.01, p=0.51) or BMI and Ki-67 (r = 0.12, 95% CI -0.06-0.29, p=0.18). When we compared BMI categories, there were no significant differences in Ki-67 (p=0.098) or sTILs % (p=0.735). However, there was a trend towards higher Ki-67 and lower sTILs % in the patients with obese BMI as compared to those with normal or overweight BMI. Median Ki-67 % was 11.9, 11.9, and 16.2 for patients with normal BMI, overweight BMI, and obese BMI, respectively. Median sTILs % was 5, 5, and 3.2 for patients with normal BMI, overweight BMI, and obese BMI, respectively. When grouped by normal/overweight BMI versus obese BMI, Ki-67 was significantly higher in the obese BMI group (11.9 vs. 16.2, p=0.033). Conclusion: Tumors of HR+ HER2-negative breast cancer patients with BMI in the obese range had significantly higher Ki-67 compared to tumors of patients with lower BMI. Ki-67 correlated with sTILs %; however, we did not identify a significant association between BMI and sTILs %. These findings suggest that BMI 30 might be associated with a more aggressive luminal B subtype of HR+ HER2-negative breast cancer, but it might not be a useful predictive biomarker of benefit of immune checkpoint inhibitor therapy. Larger patient cohorts are needed to validate and clarify these findings. References [1] Wang Z, Aguilar EG, Luna JI, et al. Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade. Nat Med. 2019;25(1):141-151. doi:10.1038/s41591-018-0221-5 [2] Calculate your body mass index. Accessed 17 May 2024. https://www.nhlbi.nih.gov/health/educational/lose_wt/BMI/bmi-m.htm Citation Format: Tanmayi Pai, Rhonda Ly, Yaohua Ma, Saranya Chumsri, Miglena K. Komforti. Association Between Ki-67, Body Mass Index, and Stromal Tumor-Infiltrating Lymphocytes in Hormone Receptor-Positive, HER2-Negative Breast Cancer Patients [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-04-17.

Abstract P1-03-30: Genomic risk score distribution and outcomes of patients with early-stage breast cancer diagnosed during pregnancy

2025-06-13

Guilherme Nader Marta , Yue Zheng , Kate E. Dibble +7 more | Clinical Cancer Research

Abstract Background: Breast cancer (BC) diagnosed during pregnancy has been associated with worse prognosis, potentially due to pregnancy-associated changes in the local and systemic hormonal and immune environments, and cytokine … Abstract Background: Breast cancer (BC) diagnosed during pregnancy has been associated with worse prognosis, potentially due to pregnancy-associated changes in the local and systemic hormonal and immune environments, and cytokine profiles. Oncotype DX Breast Recurrence Score® test is a prognostic biomarker, predictive of chemotherapy benefit in patients (pts) with early-stage, estrogen receptor-positive (ER+), HER2-negative (HER2-) BC, though there are limited data regarding its use in pregnant women. The aim of this study was to evaluate the distribution of Recurrence Score® (RS) results and the long-term outcomes of pts with ER+, HER2- BC diagnosed during pregnancy. Methods: Women with stage I-III, ER+, HER2- BC diagnosed during pregnancy were identified from a prospective cohort study of pts newly diagnosed with BC at age ≤40 years, enrolled from 2006 to 2016. Pts were classified as pregnant or not pregnant at the time of BC diagnosis. The non-pregnant group was subdivided into nulligravid or in the postpartum period. RS were obtained from banked samples when not clinically performed. RS results were classified as low (&lt;11), intermediate (11-25) or high (&gt; 25) and were correlated with clinicopathological characteristics and outcomes. Descriptive analyses were summarized for pts characteristics. RS results were compared by Wilcoxon Rank Sum test. Distant recurrence-free interval (DRFI) was estimated with Kaplan-Meier methods. Results: From 403 pts with stage I-III, ER+, HER2- BC, with clinical or research-obtained RS results and available gravidity history, 16 (4.0%) were pregnant and 387 (96.0%) were not pregnant at BC diagnosis (117 [29.0%] nulligravid and 270 [67.0%] postpartum). Median follow-up was 11.1 years. Median age at diagnosis was 36 and 37 years, node positivity (N+) rate was 8 (50.0%) and 146 (37.7%), and chemotherapy was administered to 15 (93.8%) and 276 (71.3%) pregnant and non-pregnant women, respectively. Among pts diagnosed during pregnancy, 15 (93.8%) had had prior pregnancies and 5 (31.3%) were diagnosed with stage I, 7 (43.7%) with stage II, and 4 (25%) stage III BC. From those with N+ BC, 6 pts (37.5%) had N1, and 2 pts (12.5%) had N2 disease. Within the pregnant group, median RS was 30.5 (range 21-68), with 6 (37.5%) pts having an intermediate RS and 10 (62.5%) a high RS. This contrasts with non-pregnant patients whose median RS was 20 (3-77, P=0.0002). The 11-year DRFI rates for pregnant pts with node-negative BC were 100% for RS 11-25 and 75% for RS &gt; 25; while for N+ BC, 11-year DRFI was 100% for RS 11-25 and 50% for RS &gt; 25. Conclusion: Pts with early-stage, ER+ BC diagnosed during pregnancy had genomically intermediate- or high-risk tumors. RS results were higher among pregnant pts compared to non-pregnant women. Most pregnant pts had prior pregnancies, which may have influenced the biological characteristics of the BC diagnosed during a subsequent pregnancy. Although most pregnant patients received chemotherapy, distant relapse rates were elevated among pts with high RS. Citation Format: Guilherme Nader-Marta, Yue Zheng, Kate E. Dibble, Shoshana M. Rosenberg, Erica L. Mayer, Philip D. Poorvu, Kathryn J. Ruddy, Laura C. Collins, Jeffrey Peppercorn, Lidia Schapira, Virginia F. Borges, Christy A. Russell, Steven E. Come, Ellen Warner, Kornelia Polyak, Eric P. Winer, Ann H. Partridge. Genomic risk score distribution and outcomes of patients with early-stage breast cancer diagnosed during pregnancy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-03-30.

Abstract P3-02-07: Breast Cancer Polygenic Risk Score and Patient Survival Outcomes Among Caucasians

2025-06-13

Arya Mariam Roy , Nur Zeinomar , Haiyang Sheng +7 more | Clinical Cancer Research

Abstract Introduction: Genome-wide association studies have identified many common, low-penetrance variants associated with breast cancer risk. This has led to the development of polygenic scores (PGS) to aggregate the effects … Abstract Introduction: Genome-wide association studies have identified many common, low-penetrance variants associated with breast cancer risk. This has led to the development of polygenic scores (PGS) to aggregate the effects of individual variants for risk prediction. However, the genetic determinants of breast cancer-related outcomes remain largely unknown. We hypothesize that breast cancer patients with high PGS are at an increased risk of experiencing a second breast-related adverse event, such as recurrence, contralateral breast cancer, or death. Methods: The study is based on the Pathways Study, which is a prospective cohort study of breast cancer survivors enrolled shortly after diagnosis in 2006-2013 at Kaiser Permanente Northern California, with ongoing follow-up. Genome-wide genotype data were available from 3,995 patients for calculation of 4 PGS, including PGS313, PGS4k, PGS5k and PGS6m. Scores were categorized into tertiles to investigate their associations with 7 survival outcomes including recurrence, contralateral second primary breast cancer, other second primary cancer, and death. Hazard ratios (HR) and 95% confidence intervals (CI) were derived from multivariable Cox proportional hazards regression models. The models were adjusted for age at diagnosis, race and ethnicity group, tumor stage, tumor grade, IHC subtype, surgery, radiotherapy, chemotherapy, and endocrine therapy. Results: The median age at diagnosis was 60 (23.6-94.8) years and most (68%, n= 2696) patients self-identified as Non-Hispanic whites. Many women had estrogen receptor (ER)+ (83.4%), stage I and II tumors (89%), with 13.3% HER2+ tumors. The majority (60%) received lumpectomy and some type of adjuvant therapy (44.3% radiotherapy, 47.0% chemotherapy, and 74.6% received hormonal therapy). By December 31, 2021, the median follow-up time was 10.5 (0.2-14.2) years. In the overall cohort, there were 504 recurrences, 419 total second primary cancers (146 contralateral and 237 non-breast), and 762 deaths (352 breast cancer-specific). Among Non-Hispanic whites, there were 333 recurrences, 322 total second primary cancers (113 contralateral and 184 non-breast), and 558 deaths (224 breast cancer-specific). In the overall cohort, breast cancer patients with high (T3) PGS313 had a higher risk of recurrence (HR 1.29, 95% CI: 1.02-1.61, p=0.04), all-cause death (HR 1.28, 95% CI: 0.96-1.31, p=0.03), total breast cancer events (HR 1.29, 95% CI: 1.04-1.54, p=0.02) and invasive breast cancer events (HR 1.34, 95% CI: 1.09-1.63, p=0.006) compared to those with low (T1) PGS313. Although breast cancer-specific death was observed to be higher among those with high PGS313 in the overall cohort, it was not statistically significant (HR 1.34, 95% CI: 0.99-1.73, p=0.007). In the subgroup analysis, it was observed that Non-Hispanic White breast cancer patients with high (T3) PGS313 had similar higher risk of recurrence (HR 1.29, 95% CI: 1.06-1.83, p=0.04) but not contralateral breast cancer (HR 1.22, 95% CI: 0.76-1.94, p=0.58) or other second primary cancers (HR 1.01, 95% CI: 0.77-1.34, p=0.86). They also had a higher risk of all-cause death (HR 1.30, 95% CI: 0.99-1.41, p=0.04), breast cancer-specific death (HR 1.53, 95% CI: 1.08-2.15, p=0.03), and invasive breast cancer (HR 1.33, 95% CI: 1.06-1.71, p=0.02). The other three PGS were not associated with survival outcomes in either the overall or Non-Hispanic White cohorts examined. Conclusions: Breast cancer patients with higher PGS313 scores were found to have an elevated risk of recurrence, invasive breast cancer events, and death. These results suggest that breast cancer PGS may have additional prognostic utility in patients diagnosed with the disease, indicating the need for further investigation. Citation Format: Arya Mariam Roy, Nur Zeinomar, Haiyang Sheng, Janise M. Roh, Cecile A. Laurent, Isaac J. Ergas, Jennifer Delmerico, Qianqian Zhu, Marilyn L. Kwan, Lawrence H. Kushi, Christine B. Ambrosone, Song Yao. Breast Cancer Polygenic Risk Score and Patient Survival Outcomes Among Caucasians [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-02-07.

Abstract P4-11-28: Breast Cancer Recurrence Risk Stratification with the 21-Gene Recurrence Score Assay - the Portuguese National Experience

2025-06-13

Diana Pessoa , Joana Luís , Diogo Alpuim Costa +7 more | Clinical Cancer Research

Abstract Introduction: The 21-gene recurrence score assay (RSA), a genomic tool to personalize therapy, avoiding over and undertreatment of breast cancer (BC) patients (pts), is available in Portugal since 2012. … Abstract Introduction: The 21-gene recurrence score assay (RSA), a genomic tool to personalize therapy, avoiding over and undertreatment of breast cancer (BC) patients (pts), is available in Portugal since 2012. We aimed to characterize the population of pts with BC whose tumors were tested from 2012 until Dec 2021, analyzing prescription patterns and invasive disease-free survival (iDFS). Methods: Observational, multicenter nationwide retrospective cohort study of pts with RH+/Her2-neg invasive BC treated by upfront surgery, in whom the RSA was performed. The cohort was identified by the national representative of the RSA manufacturer and clinical data was retrospectively collected from medical records by independent investigators. Results: 1119 pts from 36 centers were preregistered. We weren’t able to retrieve data from 7 patients; 21 pts were excluded due to insufficient clinical-pathological information; 7 were excluded for insufficient tissue, and 1 was staged pN2. Thus 1083 pts (91%) were included in the analysis: pN0 - 832 pts (76,8%), pN1 - 238 pts (22%) and pNx -13 pts (1,2%). In pN0 group 57.2% of pts were postmenopausal. Tumors were mostly no special type (NST, 76.6%), G2 (82.9%), with median (med) expression levels of ER 100%, PR 80% and Ki67 25%, pT1 (66.1%), Luminal B like (72.7%) and MINDACT clinical low risk (64.7%). The med RS was 17 (range 0-61). After publication of the TAILORx trial there was an increase in the number of tests per unit of time (248 vs 584); pts and tumor characteristics were similar but for pts &gt; 50 yo with RS ≤ 25 (n= 412) there was an increase in the percentage of pts that didn’t receive adjuvant chemotherapy (ACT, 79.3% vs 96%); for pts ≤50 yo with tumor RS 16 to 25 (n=137) there was an inversion in the percentage of pts treated with ACT (before TAILORx CT 62.2%; after 30%); after TAILORx, 22 of 70 pts ≤50 yo (31.4%) with tumor RS 16-25 who did not receive ACT, received adjuvant ovarian suppression. In pN1 group 64.7% pts were postmenopausal. Tumors were mostly NST (76.5%), G2 (77.3%), with med expression levels of ER 100%, PR 80% and Ki67 17.5%, pT1 (61.8%), Luminal B like (55.5%), high MINDACT risk (85.7%) and with only one positive lymph node (81.9%). The med RS was 15 (range 0-63). 237 of the 238 pts with pN1 disease had the RSA requested before publication of the RxPONDER trial results. 74% of pN1 premenopausal pts with RS ≤ 25 did not receive ACT; 8 of these 54 pts (14.8%) received ovarian suppression. With a med follow-up of 29 months and 16 pts (1,5%) lost to follow up, there were 24 (2%) invasive disease recurrences (17 pN0, 6 pN1 and 1 pNx): 14 distant, 6 locoregional, 3 both and 1 contralateral. Among pN0 pts, 9 pts were premenopausal (med tumor RS of 17, range 7-21), and 2 had received ACT; of the 8 postmenopausal pts (med tumor RS of 25.5, range 10-44), 3 pts had received ACT. 6 pN1 pts recurred - 3 premenopausal with tumor RS of 9, 14 and 15 (1 treated with ACT) and 3 postmenopausal with tumor RS of 23, 28 and 29 (the last 2 treated with ACT). Discussion/Conclusion: In this national cohort, the RSA was requested in mostly hormone receptor (HR)-strongly positive, good prognosis, BC with low risk of early recurrence disease. Pts characteristics are similar to the general characteristics of TAILORx and RxPONDER studies. The analysis of TAILORx suggested potential benefit of ACT in women ≤ 50 yo with tumours RS 16-25; however it did not result in more frequent prescription of ACT after July 2018. There was a high proportion of pN1 premenopausal pts with RS ≤ 25 that did not receive ACT (74%) but almost all pts were tested before the publication of RxPONDER. These results show that real-world studies at a national level are fundamental to evaluate clinical practice, analysing adherence to treatment recommendations and measuring pts outcomes. Citation Format: Diana Pessoa, Joana Luís, Diogo Alpuim Costa, Mário Fontes e Sousa, Idília Pina, Débora Cardoso, Isabel Andrade, Joana Simões, Ana Ferreira, Renato Cunha, Diogo Branco, José Luís Passos Coelho, for the Portugal "21-Gene Recurrence Score Assay" National Cohort Study. Breast Cancer Recurrence Risk Stratification with the 21-Gene Recurrence Score Assay - the Portuguese National Experience [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-11-28.

Abstract P2-08-09: Predictors of inadequate ovarian function suppression (OFS) in premenopausal women with hormone receptor (HR)-positive breast cancer receiving a gonadotropin-releasing hormone (GnRH) agonist in combination with endocrine therapy

2025-06-13

Maryann Kwa , Leyla Bayat , Nancy Chan +5 more | Clinical Cancer Research

Abstract Background: In premenopausal women with early-stage hormone receptor (HR)-positive breast cancer and a higher risk of recurrence, the addition of ovarian function suppression (OFS) to endocrine therapy has been … Abstract Background: In premenopausal women with early-stage hormone receptor (HR)-positive breast cancer and a higher risk of recurrence, the addition of ovarian function suppression (OFS) to endocrine therapy has been shown to improve disease outcomes, as demonstrated by combined analysis of the SOFT/TEXT trials. Estradiol (E2) is the primary source of estrogen in premenopausal women and is synthesized from the ovaries through indirect control of gonadotropin-releasing hormone (GnRH). Endocrine therapy with a GnRH agonist has become a mainstay of treatment in premenopausal women for ovarian suppression. However, studies have shown that up to 25% of patients do not achieve adequate ovarian suppression within the first year of treatment. Data remains limited regarding whether monitoring of OFS should routinely be performed and is not part of current NCCN guidelines. The aim of our study was to evaluate premenopausal women in a ‘real world’ setting at our institution who did not achieve adequate OFS and to assess potential contributing factors. Methods: This was a retrospective, descriptive study of premenopausal women ≥18 years of age at our institution from 2020-2022 with stage I-III HR-positive breast cancer receiving OFS in combination with endocrine therapy with either an aromatase inhibitor or tamoxifen. OFS was achieved by use of a GnRH agonist with leuprolide or goserelin. Patients who had two or more consecutive tests showing non-suppressed estradiol levels (E2 level &gt;20 pg/mL) were considered to have inadequate ovarian suppression. Data regarding patient age at the start of treatment, BMI, receipt of neoadjuvant and/or adjuvant chemotherapy, history of prior pregnancies, history of diabetes mellitus, and choice of initial GnRH agonist were examined. The rate of change to another GnRH agonist upon ovarian suppression failure was also determined. Results: Twenty-six patients (age range: 27-50) were identified at our institution who received either leuprolide or goserelin. Of these patients, 25 received OFS every month (96%) and 1 received OFS every three months (4%). The rate of inadequate OFS among all patients was 30.8%. The average age at the start of treatment was 40.1 years for those with adequate OFS compared to 37.9 years for those with inadequate OFS. Average BMI was 26.7 in the adequate OFS group and 30.3 in the inadequate OFS group. In the adequate OFS vs. inadequate OFS group, 17% vs. 38% had received neoadjuvant chemotherapy, and 39% vs. 63% had received adjuvant chemotherapy, respectively. 17% of patients in the adequate OFS group had a history of diabetes mellitus, compared to 25% in the inadequate OFS group. In the adequate OFS versus inadequate OFS group, 33% versus 50% had a history of at least one term pregnancy, respectively. For those who received leuprolide initially, 67% had adequate OFS. In comparison, for those who received goserelin initially, 33% had adequate OFS. Among the patients with inadequate OFS, 50% had their treatment subsequently changed to the alternative GnRH agonist. Discussion: This study showed that inadequate OFS was detected in 31% of the patients, half of whom underwent a subsequent change in therapy to the alternative GnRH agonist. Patients who received leuprolide initially were more likely to have adequate OFS compared to those who received goserelin. A higher BMI, history of diabetes, and history of term pregnancy were found in patients with inadequate OFS. Further research is needed to establish monitoring guidelines for estradiol and the optimal degree of ovarian suppression for premenopausal patients receiving OFS. Citation Format: Maryann Kwa, Leyla Bayat, Nancy Chan, Arturo Orlacchio, Cigdem Karayigitoglu, Doaa Ayoubi, Tsivia Hochman, Douglas Marks. Predictors of inadequate ovarian function suppression (OFS) in premenopausal women with hormone receptor (HR)-positive breast cancer receiving a gonadotropin-releasing hormone (GnRH) agonist in combination with endocrine therapy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-08-09.

Abstract P2-12-04: Impact of Weight and Weight Variation in Adolescent and Young Adult (AYA) Women with Invasive Breast Cancer

2025-06-13

Nerea Lopetegui‐Lia , Emily C. Zabor , Kenda Alkwatli +7 more | Clinical Cancer Research

Abstract Background: Breast cancer (BC) is the most common malignancy in adolescent and young adult (AYA) women age 15-39, and the incidence continues to rise each year (1, 2). The … Abstract Background: Breast cancer (BC) is the most common malignancy in adolescent and young adult (AYA) women age 15-39, and the incidence continues to rise each year (1, 2). The reason for this remains unknown, but one potential etiology includes the increasing incidence of obesity (1). Studies in premenopausal women have demonstrated that a high body mass index (BMI) prior to BC diagnosis is associated with worse clinical outcomes (3). The prognostic value of weight gain after BC diagnosis remains unclear (4) as its impact on recurrence risk and overall survival has been inconsistently reported, with limited data among the AYA population (5). Our aim was to describe the clinical-pathological characteristics of AYA women diagnosed with BC, its association with weight change, and the impact of weight variation during the initial treatment period on patient outcomes. Methods: This retrospective study included patients with invasive stage I-III BC, age 15-39 at the time of diagnosis, that received treatment at the Cleveland Clinic between 1996 and 2023. Data was collected via computerized data extraction and manual chart review. The analysis was limited to patients who had both a pre-diagnosis (within 1.5 years (y) before diagnosis) and post-diagnosis (up to 1.5y after diagnosis) BMI measurement so that change in BMI could be calculated. A BMI reduction of ≥2 units was considered clinically meaningful weight loss and a BMI increase of ≥2 units was considered clinically meaningful weight gain. A change in BMI &lt; 2 units was considered no change or stable weight. Continuous and categorical variables were summarized using median IQR and N (%), respectively. The Kruskal-Wallis test was used to test for differences according to BMI change categories in continuous variables, and either Fisher’s exact test or the Chi-squared test was used to test for differences according to BMI change in categorical variables, as appropriate. The Kaplan-Meier method was used to estimate 5y overall survival (OS) probability, the log-rank test was used to test for differences according to weight change and hazard ratios (HR) were estimated using univariable Cox regression. Results: A total of 345 patients were identified for analysis. 339 patients (98%) were ≥25 years, 5 were age 19-24, and one was ≤18 years. The median pre-diagnosis BMI was 25 kg/m2 (22,31). Stable weight was observed in 242 patients (70%), 52 (15%) experienced weight loss, and 52 (15%) had weight gain during the first 1.5y of treatment from the time of diagnosis. While the measurement and analysis of weight changes focused on the initial BC treatment period, median follow-up time among survivors was 6.8y. During follow-up, 51 patients died from any cause. The 5y OS probability of patients with weight gain, weight loss, and stable weight were 66%, 85%, and 90%, respectively (log-rank P=0.006). Patients with weight gain had a statistically significant increased hazard of mortality as compared to those with no change and with weight loss combined, HR 2.71 (95% CI: 1.44-5.10), P=0.005 Discussion: Overall survival probability was reduced in AYA women with early stage BC that experienced weight gain during the initial treatment period. Approximately 70% of patients had no significant change in BMI during their initial BC treatment course, despite undergoing loco-regional and systemic therapies. These results support counselling AYA women regarding the risk of reduced survival associated with weight gain during the initial BC treatment period. Future research is necessary to examine the impact of longer-term weight changes on the risk of BC recurrence and mortality. Citation Format: Nerea Lopetegui-Lia, Emily C. Zabor, Kenda Alkwatli, Ahmed Mohamed, Hassan Elmaleh, Alex Milinovich, Anukriti Sharma, Blaine Martyn-Dow, Kevin M Pantalone, Daniel Rotroff, Halle CF Moore. Impact of Weight and Weight Variation in Adolescent and Young Adult (AYA) Women with Invasive Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-12-04.

Abstract P2-10-29: Cascade Testing in Racially/Ethnically Diverse Relatives of Patients with Breast or Ovarian Cancer (CASSIE)

2025-06-13

Alissa Michel , Nicole Collins , Erik Harden +6 more | Clinical Cancer Research

Abstract Background: About 5-10% of breast cancers and 15% of ovarian cancers are attributed to germline pathogenic variants (PVs) in genes such as BRCA1 or BRCA2. Cascade testing, the process … Abstract Background: About 5-10% of breast cancers and 15% of ovarian cancers are attributed to germline pathogenic variants (PVs) in genes such as BRCA1 or BRCA2. Cascade testing, the process of informing at-risk family members of a PV detected in the proband and offering genetic counseling/testing, is a significant public health intervention which can reduce the burden of disease through targeted early detection and prevention strategies. Several studies have demonstrated that uptake of cascade testing is low, ranging from 15-57%, with testing more commonly pursued when the proband is White. Barriers include time constraints during clinical encounters, lack of contact and emotionally distant relationships with family members, geographic barriers, fear of a positive result and medical mistrust among racially/ethnically diverse patients. To address these barriers, we have developed a patient-facing web-based decision aid (DA), RealRisks, which is available in English and Spanish and has been rigorously tested in a randomized controlled trial (RCT) of genetic testing uptake among diverse women with a family history of breast or ovarian cancer. Study Design: We are conducting a pilot cluster-RCT of the RealRisks DA and direct access to genetic counseling/testing services to increase cascade testing. We will enroll 30 probands diagnosed with breast or ovarian cancer and a known PV in a hereditary breast and ovarian cancer (HBOC) gene. They will invite 1-4 female first-degree relatives (FDRs) (60 total) who have not undergone germline genetic testing to participate. Cluster randomization will occur at the proband level with stratification based upon U.S. or foreign-born. Female FDRs will be assigned to a standard of care (SOC) notification letter alone or in combination with RealRisks and access to genetic counseling/testing services based upon randomization assignment of the proband. RealRisks consists of interactive modules to collect family history and elicit personal preferences on genetic testing. Probands and FDRs will complete surveys at baseline and 3 months. A subset of probands and FDRs will participate in semi-structured interviews to better understand barriers and facilitators to cascade testing. Eligibility criteria: Eligible probands include: 1) men or women diagnosed with Stage 0-IV breast or ovarian cancer; 2) PV in a high or moderate-penetrance HBOC predisposition gene (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, TP53) identified within the past year; 3) at least 1 female FDR who has not undergone germline genetic testing. Eligible FDRs include: 1) women, age ≥18 years; 2) FDR of patient with breast or ovarian cancer and known PV; 3) English or Spanish-speaking; 4) able to provide consent. Outcomes: Our primary endpoint is genetic testing uptake at 3 months among FDRs. Secondary endpoints include genetic testing knowledge, genetic testing intention/decision, informed choice and decision conflict among FDRs at baseline and 3 months. Through qualitative analysis, we will assess barriers and facilitators to communication of genetic test results to family members, experiences with RealRisks, and access to genetic counseling/testing and downstream cancer screening/preventive services. Statistical methods: We will have &gt;80% power to detect a difference in cascade testing uptake of 20% in the control arm and 60% in the intervention with a 1-sided alpha of 0.05, assuming an intraclass correlation coefficient (ICC) of under 0.20 to account for clustering and 10% dropout. Current/target accrual: The trial will be activated in August 2024. Discussion: Results from this pilot trial will inform a larger multicenter RCT to reduce disparities in cascade testing uptake for HBOC syndrome. Funding: Conquer Cancer YIA, P50MD017341 Citation Format: Alissa Michel, Nicole Collins, Erik Harden, Eileen Fuentes, June Hou, Elana Levinson, Rita Kukafka, Meghna S. Trivedi, Katherine D. Crew. Cascade Testing in Racially/Ethnically Diverse Relatives of Patients with Breast or Ovarian Cancer (CASSIE) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-10-29.

Abstract P3-02-09: Correlation between risk groups and molecular subtype of breast cancer with metabolic syndrome and ethnicity

2025-06-13

Sharda P. Singh , Chathurika S. Dhanasekara , Michael W. Melkus +7 more | Clinical Cancer Research

Abstract Background: Breast cancer (BC) is the most common malignancy among women worldwide. Comprehensive genomic profiling has been widely used to identify molecular biomarkers and signatures for developing novel therapeutic … Abstract Background: Breast cancer (BC) is the most common malignancy among women worldwide. Comprehensive genomic profiling has been widely used to identify molecular biomarkers and signatures for developing novel therapeutic strategies. BC is a complex disease; besides the genomic and molecular characterization of tumors, racial/ethnic classification and body mass index (BMI) are key determinants of treatment outcomes. To explore gene-to-phenotype relationships, we obtained transcriptomic and clinical data from 978 patient samples comprising all four BluePrint® (BP) subtypes: Luminal A, Luminal B, HER-2, and Basal, representing ∼25% of each genomic subtype. We investigated the association of biomarkers of inflammation, apoptosis, oxidative stress, autophagy, and ER stress in patients with BC and correlated them with BMI, menopausal status, and ethnicity. Method: The FLEX registry (NCT03053193) enrolled 14000 patients with stage I-III BC across 90 institutions in the United States and stratified risk groups based on the 70-gene signature (MammaPrint®, (MP)) and molecular subtype based on the 80-gene signature (BP). We obtained transcriptomic (110 genes) and clinical data from 978 patient samples, representing ∼25% of each genomic subtype. Principal component analysis (PCA) was conducted using the ‘PCAtools’ package in R to reduce the gene expression data's dimensionality and identify major variation patterns among the samples. Analysis of variance (ANOVA) was performed between groups using the first five principal components (PCs). The family-wise error rate was set at 0.05, using the modified Holm-Bonferroni approach. Results and Conclusion: Of the 978 patients (Caucasians:81.7%; African Americans:2.58%; other races: 5.7%), the risk or genetic profile was as follows: MP: Ultra-Low = 76 (8%), Low = 176 (18%), High1 = 315 (32%), and High-2 = 411 (42%); BP: Luminal A 250 (26%), Luminal B = 250 (26%), HER2 = 228 (23%), and Basal = 250 (26%). The mean age was 58.84±13.04, the average BMI was 30.04±7.34, and the majority were postmenopausal (n = 717, 73%). The first five PCs accounted for 63.11% of the total variance of the dataset. These five PC loadings (variable contributes) were enriched for genes associated with various cellular mechanisms, including glucose metabolism, cellular growth, resistance to cell death, angiogenesis induction, oxidative stress handling, and epigenetic modifications. Interestingly, the pairs plot comparing PC1 through PC5 showed a certain degree of clustering and PC4 (total variance of 4.59%) indicated distinct clustering for each molecular subtype. The biplot for PC1 and PC4 showed a certain degree of separation when intrinsic molecular subtypes and risk of recurrence categories were used. SOD2, KLK5, KLK7, and IL8 showed a strong positive correlation with PC4, whereas GLI1 showed a strong negative correlation with PC4. The loading plot also showed a positive loading for SOD2, indicating a significant role of SOD2 in differentiating distinct molecular subtypes. Comparisons of PCs with clinical variables showed that PC4 was significantly correlated with all baseline clinical variables, including age (p &lt; 0.001), BMI (p = 0.001), race (p &lt; 0.001), menopausal status (p = 0.001), molecular subtype (p &lt; 0.001), and risk of recurrence (p &lt; 0.001). Additionally, PC4 was also found to be significantly correlated with tumor size (p &lt; 0.001), lymph node status (p &lt; 0.001), and the presence of distant metastasis (p &lt; 0.001). In conclusion, our findings demonstrate that genes in PC4 play a crucial role in discriminating known molecular profiles when different risk categories, as it is significantly associated with baseline characteristics, and risk of recurrence. Further analysis should be conducted to explore genes that contribute to PC4, such as SOD2. These results highlight the potential of SOD2 as a prognostic biomarker and a therapeutic target in breast cancer. Citation Format: Sharda P. Singh, Chathurika Samudani Dhanasekara, Michael W. Melkus, Reshad S. Ghafouri, Soroush Shahrokh, Flavia Sardela de Miranda, Maria F. Mahecha, Adam Brufsky, Joyce O'Shaugnessy, VK Gadi, Cathy Graham, Mehran Habibi, William Audeh, Sahra Uygun, Lavanya Samraj, Rakhshanda Layeequr Rahman. Correlation between risk groups and molecular subtype of breast cancer with metabolic syndrome and ethnicity [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-02-09.

Abstract P2-01-09: Patient-reported outcomes in premenopausal breast cancer patients with or without ovarian suppression therapy – a subgroup analysis from a Brazilian prospective cohort

2025-06-13

Natalia Cristina Cardoso Nunes , Giselle de Souza Carvalho , Lilian Campos Caldeira Lerner +7 more | Clinical Cancer Research

Abstract Background: Young women with breast cancer (BC) treated with chemotherapy or endocrine therapy (ET) often experience physical and psychosocial changes during treatment, partly due to non-physiological menopausal symptoms. These … Abstract Background: Young women with breast cancer (BC) treated with chemotherapy or endocrine therapy (ET) often experience physical and psychosocial changes during treatment, partly due to non-physiological menopausal symptoms. These symptoms tend to be worse with ovarian function suppression (OFS), and it can significantly affect the quality of life (QoL), leading to nonadherence to treatment. Our study aims to assess patient-reported outcomes (PRO) in premenopausal breast cancer patients receiving or not OFS. Methods: This report is a sub-analysis of our institutional multicenter, prospective, observational study involving female patients with BC who received treatment in private healthcare facilities in the Brazilian states of Rio de Janeiro and São Paulo. For this analysis, we focused on patients aged 50 years or younger with stage I to III invasive breast cancer who underwent adjuvant ET between 01/01/2013 and 01/31/2023. Patients were divided based on whether they received OFS. PRO was evaluated through EORTC-QLQ-BR23 functional scales at baseline, 3, 6, 9, 12, and 24 months. Patients were included before any systemic treatment, including chemotherapy. We used linear mixed models with adjustments for the cancer stage to compare the scales between the two groups. Results were reported relative to the baseline category, using 95% confidence intervals and p-values. The R software, version 4.1.2, was used for the analyses. Results: In total, 363 patients met the inclusion criteria. Of these, 290 received ET alone, and 73 were assigned to receive OFS+ ET. Patients who received OFS were more likely to be younger (64.4% vs. 25% &lt;40 years), had a more advanced cancer stage (31% vs. 13% stage III), and were more likely to receive chemotherapy (90.4% vs. 73.4%). The number of patients who completed the questionnaires was 363, 152, 272, 250, 252, and 171 at baseline, 3, 6, 9, 12, and 24 months, respectively. Regarding the functional scales “sexual functioning” and “sexual enjoyment,” despite the absence of statistical significance between groups, the OFS group experienced a more pronounced clinically significant (&gt;10 points) decrease in the first 6 months of treatment and an inability to return to baseline after 24 months. At months 6 and 12, a higher number of sexually active patients reported not having sexual desire or satisfactory sex. Furthermore, after 24 months of treatment, patients in the OFS group were more likely to report hot flashes, headaches, being physically less attractive, less feminine, less sexual interest, and less sexual activity. Conclusion: Despite OFS contributing to improved disease-free survival and overall survival in adjuvant treatment, its side effects significantly affect the patient's long-term QoL. Discussing these side effects with patients before starting systemic therapy and developing treatment plans is crucial to enhance the QoL of patients dealing with OFS-related concerns. Our study emphasizes the need for a personalized, empathetic approach to patient care and regular sexual health assessments by oncology healthcare professionals. Citation Format: Natalia Cristina Cardoso Nunes, Giselle de Souza Carvalho, Lilian Lerner, Gustavo Queiroz Di Giusto, Paola Kelly Martins dos Santos, Amanda Soares Gonçalves, Perla de Mello Andrade, Juliana Pompeu Pecoraro, Carolina Galvão Teixeira, Mariana Ribeiro Monteiro. Patient-reported outcomes in premenopausal breast cancer patients with or without ovarian suppression therapy – a subgroup analysis from a Brazilian prospective cohort [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-01-09.

Abstract P2-03-06: Factors Associated with Pregnancy and Postpartum Treatment After Endocrine Therapy Interruption in Breast Cancer Patients

2025-06-13

Risa Kasahara , Atsuko Kitano , Kumiko Kida +5 more | Clinical Cancer Research

Abstract Background: We previously retrospectively analyzed the long-term prognosis of patients who interrupted endocrine therapy in an attempt to achieve pregnancy after breast cancer treatment. We reported that there was … Abstract Background: We previously retrospectively analyzed the long-term prognosis of patients who interrupted endocrine therapy in an attempt to achieve pregnancy after breast cancer treatment. We reported that there was no significant difference in the risk of breast cancer related events between the endocrine therapy interruption and continuation groups (at 110 months postoperatively were 25.7% in the continuation group vs. 20.0% in the interruption group, p = 0.5). The study also reported that 58% of the patients in the interruption group became pregnant (14.6% in the continuation group, p&lt;0.05), indicating that interruption of endocrine therapy is significantly increases pregnancy rates. In this study, we aimed to examine factors that predispose to pregnancy after interruption of endocrine therapy and postpartum breast cancer treatment. Methods: This was a retrospective study using surveying of medical chart data between June 2007 and November 2015 at St. Luke’s International Hospital. Patients with stage I-III ER-positive breast cancer who visited a reproductive center before starting treatment for breast cancer and interrupted endocrine therapy for less than 120 months were included in this study. Patients who attempted to conceive after discontinuing endocrine therapy were divided into two groups: those who became pregnant and those who did not. The factors associated with achieving pregnancy and postpartum treatment were compared between the two groups. Statistical analysis was performed using the chi-square test and t-test.[Result] Patients who interrupted treatment within 120 months of endocrine therapy and became pregnant were 20/33 patients (60.1%). The median age was 35 years in the pregnancy group and 40 years in the non-pregnancy group. In the pregnancy group, 18 patients (90%) were 39 years old or younger, and in non-pregnancy group, 7 patients (53.8%) were 39 years old or younger (p&lt;0.05). The number of patients who were married or had a partner was 16 (80%) in the pregnancy group and 11 (85%) in the non-pregnancy group. Chemotherapy was administered in 9 (45%) of the pregnancy group and 6 (46.2%) of the non-pregnancy group and GnRHa for fertility purpose during chemotherapy was used for four patients (4/9, 44.4%) in the pregnancy group and two patients (2/6, 33%) in the non-pregnancy group. Fertility procedures included duplicate cases: 17 cases preserved embryos (85%) and 5 preserved oocytes (25%) in the pregnancy group, 8 cases preserved embryos (61.5%), 3 preserved oocytes (23.1%), 2 preserved ovaries (15.4%) and 1 (7.7%) could not be frozen in the non- pregnancy group. Of the 20 cases in the pregnancy group, 18 had delivered and 20 children were born. (Two cases gave birth twice.) and two were currently in the process of conceiving. The median time from interruption of endocrine therapy to delivery was 23 months (median); 21 months for those under 35 years of age and 27 months for those 35-40 years of age. Endocrine therapy was resumed after delivery in 9 cases (9/20, 45%), with a median of 8 months (0-19 months) between delivery and resumption of endocrine therapy. The 11 cases who did not resume endocrine therapy after childbirth included 6 cases who had completed 5 years of endocrine therapy, 2 cases who did not resume endocrine therapy because their hormone receptors were originally weakly positive, and 3 cases for unknown reasons. Discussion and Conclusion:Pregnancy after interruption of endocrine therapy was significantly associated with age &lt;35 years at the time of fertility preservation. This age factor was not related to other factors. While many patients resumed endocrine therapy after delivery, there were instances of non-resumption, highlighting the need for clearer guides and communication regarding postpartum treatment decisions. The findings can inform clinical practice and patient counseling regarding fertility preservation and treatment decisions. Citation Format: Risa Kasahara, Atsuko Kitano, Kumiko Kida, Fumi Akitani, Kyoko Shiota, Asaka Wada, Junko Takei, Atsushi Yoshida. Factors Associated with Pregnancy and Postpartum Treatment After Endocrine Therapy Interruption in Breast Cancer Patients [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-03-06.

Abstract P4-03-01: Alarming levels of obesity and overweight in Brazilian women with early-stage ER+ breast cancer in adjuvant endocrine therapy

2025-06-13

Daniele Xavier Assad , Danielle Laperche dos Santos , Fernanda Cesar Moura +7 more | Clinical Cancer Research

Abstract Background: Adiposity and the presence of overweight/obesity are associated with mortality in general and also with mortality and recurrence related to breast cancer. This study aims to evaluate obesity … Abstract Background: Adiposity and the presence of overweight/obesity are associated with mortality in general and also with mortality and recurrence related to breast cancer. This study aims to evaluate obesity and overweight levels in Brazilian women with early-stage ER+ breast cancer in adjuvant endocrine therapy and its relations with clinical and demographic charactheristics. Methodology: Women with a history of early-stage ER+ invasive carcinoma of the breast on adjuvant ET for at least 6 months were invited to participate of this study. Body Mass Index (BMI) were assessed according to the cutoff points proposed by the World Health Organization (1998). Adherence, quality of life, sexual dysfunction and return to work were also assessed. Patients were stratified according to Body Mass Index (BMI (Eutrophy: 18.5 to 24.9kg/m2, Overweight: 25 to 29.9kg/m2 and Obesity: &gt;=30kg/m2). To investigate statistically significant differences between groups, Pearson's Chi-Square tests were used. To evaluate the relationship between variables and BMI in patients with breast cancer, multinomial logistic regression analysis was used. Results: From June 2021 to March 2024, 557 women from 11 Brazilian institutions were recruited. Mean age was 62 y.o , mean tumor size was 2.14 cm, mean duration of ET was 3.1y. A total of 27% of patients were obese, 42% were overweight and 30.8% had eutrophy. Women with higher education had a lower prevalence of obesity (26%) compared to those with lower education (31%) (p = 0.03). The presence of comorbidities had a highly significant association with BMI, with a higher prevalence of comorbidities among obese women (33%) compared to those with ideal weight (24%) (p &lt; 0.001). Patients treated in public hospitals had a higher prevalence of obesity (35%%) compared to those treated in private hospitals (20%) (p &lt; 0.001). Patients in stage III were more likely to be obese (odds ratio = 2.88, 95% CI: 1.55-5.33, p &lt; 0.001) compared to those in stage I. There was no significant association between BMI and variables such as age (p = 0.97), ethnicity (p = 0.35), marital status (p = 0.98), and duration on endocrine therapy (p = 0.17). Better QLQ C30 - Physical Functioning was associated with a lower chance of obesity (odds ratio = 0.95, CI95%: 0.93-0.97, p &lt; 0.001) and overweight (odds ratio = 0.96, CI95 %: 0.94-0.98, p &lt; 0.001). Arm Symptoms also showed a significant association with obesity (odds ratio = 1.01, 95% CI: 1.00-1.02, p = 0.005), but not with overweight (odds ratio = 1.00, 95% CI: 0.99-1.01, p = 0.082). In multivariate analysis, stage III disease (OR 1.72), prior lumpectomy (OR 7.2), prior mastectomy (OR 2.7), axillary lymphonode dissection (OR 2.8) and use of concomitant medication (OR 1.8) were related to obesity. Conclusions: Only a third of the women evaluated in the study had an adequate BMI, leading to a worrying risk of morbidity such as cardiovascular disease and risk of breast cancer relapse. Some characteristics related to obesity, such as its greater presence in patients treated in the public service and in women with a lower level of education, lead to the hypothesis that economic factors may be related to this disease. Citation Format: Daniele Assad-Suzuki, Danielle Laperche-Santos, Fernanda Cesar Moura, Sulene Cunha Sousa Oliveira, Andrea Kazumi Shimada, Renata Arakelian, Anna Luiza Zapalowski Galvão, Bruno Santos Wance de Souza, Amanda Guimarães Castro, Monalisa Ceciliana Freitas Moreira de Andrade, Yuri Cardoso Rodrigues Beckedorff Bittencourt, Maria Cristina Figueroa Magalhães, Poliana Albuquerque Signorini, Daniela Jessica Pereira, Angélica Nogueira-Rodrigues, Romualdo Barroso-Sousa. Alarming levels of obesity and overweight in Brazilian women with early-stage ER+ breast cancer in adjuvant endocrine therapy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-03-01.

Abstract P2-01-01: Lifestyle Linked Biomarker is Associated with Poor Prognosis in Estrogen Receptor Negative Breast Cancer

2025-06-13

Lindsay L. Peterson , Tao Yu , Jingqin Luo +4 more | Clinical Cancer Research

Abstract Background: Advanced glycation end-products (AGEs), reactive metabolites produced as a by-product of sugar metabolism, have been linked to higher breast cancer (BC) risk and increased mortality after BC diagnosis. … Abstract Background: Advanced glycation end-products (AGEs), reactive metabolites produced as a by-product of sugar metabolism, have been linked to higher breast cancer (BC) risk and increased mortality after BC diagnosis. The total body AGE pool is composed of endogenous AGEs and exogenous AGEs (consumed mainly through processed and fried foods common in Westernized diets). Diets high in AGEs have been linked to BC risk and outcomes. In our prior work, we reported that higher serum AGE (sAGE) levels, a reflection of total body AGE, are associated with reduced overall and BC-specific survival. sAGE was positively associated with BMI (p&lt;.0001, rs = 0.10) and negatively associated with physical activity (p&lt; .001, rs = -0.06). Comparing the highest quintile to the lowest quintile, sAGE was negatively associated with all survival outcomes in the entire cohort (overall survival (OS) HR=1.66 p=.014, recurrence free survival (RFS)=1.66 P=.004, BC specific survival (BCSS) HR=1.78 p=.013, distant metastasis free survival (DMFS) HR=1.81 p=.004). Here we explore the relationship between sAGE and BC outcomes by hormone receptor status in the Women’s Healthy Eating and Living (WHEL) study. Methods: The WHEL randomized 3088 BC patients stage I-III who completed their primary therapy to a high-vegetable, low-fat diet or control and followed for a median of 7.3 years. Main outcomes were invasive BC events (recurrence or new primary N=518), death due to BC (N=262) and deaths from any cause (N=315). Fasting blood was collected at study entry. sAGE was measured as the AGE metabolite carboxymethyllysine (ug/ml). sAGE was log transformed and corrected for plate batch effect via linear regression, and analyzed in continuous scale and in quintiles. The relationship between sAGE and survival endpoints was calculated using Kaplan-Meier and Cox regression models. In multivariable Cox models, we evaluated the interaction between sAGE (in quintiles) and ER or ER/PR status, adjusting for potential confounding covariates (age, race, BMI, smoking, alcohol use, physical activity, tumor characteristics). Results: 2564 participants had sAGE available. After excluding samples for excessive variabilities, 2315 samples were analyzed. Patient characteristics: median age 52, 85% white, 79% menopausal, 70% received chemotherapy, 43% node positive, 71% stage II or III. 1727 patients were ER+ and 556 were ER-. Raw corrected sAGE ranged from 0.0-48.15 ug/ml (median 7.39); logged and corrected ranged from -5.04-1.67. In the multivariable Cox model, the main effects of sAGE were significant for all the survival endpoints (OS p=0.023, RFS p=0.042, DMFS p=0.012, BCSS p=0.028), as well as the sAGE and ER interaction effects (OS p=0.017, RFS p=0.011, DMFS p=0.015, BCSS p=0.008). The strongest associations between sAGE and BC outcomes were seen within ER- cases: ER- patients of the highest sAGE quintile showed significantly higher risk compared to those with the lowest quintile (OS HR=2.37 p=.02, RFS HR=2.02 p=.02; BCSS HR=2.74 p=.01, DMFS HR=2.62 p=.01). Among the patients with the highest quintile sAGE, ER- cases showed consistently higher risk than ER+ (OS HR=1.83 p=.03, RFS HR=1.78 p=.02; BCSS HR 2.39 p=.004, DMFS HR=1.58 p=.11). Similar but slightly less significant results were seen with combined ER/PR status, likely due to the reduced sample size from missing values. Conclusions: In a cohort of women with early BC, higher sAGEs were associated with worse survival outcomes in BC, with a stronger association in ER- BC compared to ER+ BC. AGEs may represent a novel, lifestyle-linked, modifiable prognostic biomarker in ER- BC. Interventions aimed at lowering sAGE levels should be tested in this high-risk subgroup for their impact on prognostic and metabolic biomarkers as well as clinical outcomes. Citation Format: Lindsay Peterson, Yu Tao, Jingqin Luo, Graham A. Colditz, Yikyung Park, Jennifer A. Ligibel, David Turner. Lifestyle Linked Biomarker is Associated with Poor Prognosis in Estrogen Receptor Negative Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-01-01.

Abstract P5-02-15: Impact of socioeconomic factors on stage of diagnosis and mortality among breast cancer patients

2025-06-13

Yolcar Chamorro , Muni Rubens , Mukesh Roy +5 more | Clinical Cancer Research

Abstract Background: Breast cancer (BC) is the most common cancer and the second leading cause of cancer deaths among US women. From 1989 to 2017, mortality rates dropped by 40%, … Abstract Background: Breast cancer (BC) is the most common cancer and the second leading cause of cancer deaths among US women. From 1989 to 2017, mortality rates dropped by 40%, largely attributed to the widespread adoption of mammogram screening and advancements in treatment. However, disparities persist with Black women experiencing 40% higher mortality than White women. Delays in diagnosis due to limited access to screening and treatment contribute to this disparity. Social determinants of health further impact the accessibility and quality of healthcare received. This study examines socioeconomic influences on BC stage at diagnosis and mortality. Methods: We conducted a retrospective analysis of data from the National Cancer Database (NCDB), a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. All female patients (pts) ≥18 years with a diagnosis of stage 0-IV breast cancer (BC) treated from 2004 to 2020 were included. Race/ethnicity included White (W), Black (B), Hispanic (H), and Other (O). Income and education were categorized into quartile (Q) I, II, III, and IV from lowest to highest per NCDB definitions. Kaplan Meier analysis with log rank test was done to compare the overall survival from diagnosis and Cox proportional analysis was done to estimate hazard ratio. Results: A total of 1,826,818 pts were included in the analysis. Of these, 79.5% were White (W), 11% Black (B), 4.9% Hispanic (H), and 4.6% Other (O) that includes (Asian, American Indian, and other). Overall, most pts were in income and education Quartile 4 (38.1% and 42.4%). W pts had a higher proportion of stage I disease at diagnosis (47%) when compared to B (35.6 %) and H (38.2%) pts (p&lt;0.001). In contrast, W had a lower proportion of stage III (7.9%) when compared to B (11.2%) and H (10.7%) (p&lt;0.001). B pts had a higher proportion of stage IV (5.2%) compared to W (3%) and H (3.4%) pts (p&lt;0.001). Income Q4 had a higher proportion of stage I (46.6%) compared to Q1 (41.2%). Income Q4 had a lower proportion of stage III (7.3%) and IV (2.7%) compared to income Q1 (10.3% and 4.4% respectively). Similarly, education Q4 had a higher proportion of stage 1 (47.1%) compared to Q1 (40.3%). Education Q4 had a lower proportion of stage III (7.3%) and IV (2.7%) compared to Q1 (10.5% and 4.4% respectively). All these differences were statistically significant p&lt;0.001. Income distributions among race/ethnicity showed that W had a lower proportion in Q1 (10.9%) compared to B (38.4%) and H (22.4%). In contrast, W had a higher proportion in Q4 (40.5%) compared to B (18.2% and H (26.9%). We found similar disparities when we evaluated education distributions among race/ethnicity. Kaplan Meier analysis showed that mortality was significantly higher for B, lowest income quartile, and lowest education quartile for all stages (log rank P&lt;0.001). Cox proportional analysis showed that mortality was highest for B (HR: 1.12; 95% CI, 1.11-1.13, P&lt;0.001), lowest income quartile (HR: 1.22; 95% CI, 1.21-1.24, P&lt;0.001), and lowest education quartile (HR: 1.09; 95% CI, 1.08-1.10, P&lt;0.001). Conclusion: Results of this study show that race and ethnicity as well as pt income and education level were associated with stage of diagnosis and mortality among BC pts. Identifying barriers to accessing screening imaging and adequate BC treatment can help us develop systems that will give extra support to pts in need. Future studies should focus on developing interventions to decrease these disparities and improve outcomes. Acknowledgement: The data used in the study are derived from a de-identified NCDB file. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methodology employed, or the conclusions drawn from these data by the investigator. Citation Format: Yolcar Chamorro, Muni Rubens, Mukesh Roy, Reshma Mahtani, Naomi Dempsey, Lauren Carcas, Manmeet Ahluwalia, Ana Sandoval-Leon. Impact of socioeconomic factors on stage of diagnosis and mortality among breast cancer patients [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-02-15.

Abstract P2-03-02: Fertility and ovarian function preservation in young women with breast cancer: A comparative analysis of two prospective cohort studies in Mexico and Italy

2025-06-13

Fernanda Mesa-Chavez , Maria Grazia Razeti , Eva Blondeaux +7 more | Clinical Cancer Research

Abstract Background: Due to their age and life stage, young women with breast cancer (YWBC) encounter distinct challenges related to their diagnosis and treatment. Unmet parity along with potential premature … Abstract Background: Due to their age and life stage, young women with breast cancer (YWBC) encounter distinct challenges related to their diagnosis and treatment. Unmet parity along with potential premature ovarian insufficiency represent a notable concern among this group of patients. Effective strategies to address this issue include fertility preservation techniques, as well as temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) for ovarian protection during cytotoxic treatments. Here we report a comparative analysis of two prospective studies describing the rates and factors associated with fertility and ovarian function preservation choices in YWBC from two countries. Methods: Women with BC at an age ≤40 years were prospectively accrued in the Joven & Fuerte and PREFER multicenter cohorts in Mexico and Italy, respectively. These studies provide early referrals to fertility and/or ovarian function preservation strategies at diagnosis as needed. This analysis comprised YWBC diagnosed from 2014-2019 whose treatment included chemotherapy (CT) with the objective of identifying their uptake of fertility and ovarian function preservation options. Patients’ characteristics within and across cohorts were compared using chi-squared, Fisher’s exact, and Wilcoxon tests. Simple logistic regression was conducted to calculate the likelihood of undergoing fertility preservation. Results:In total, 485 patients were included: 361 (74%) in Mexico and 124 (26%) in Italy. Median age at diagnosis was 35 years (IQR 32-38) in both cohorts. A higher proportion of Mexican patients had a partner compared to Italian patients (65% vs 59%, p=.04). Patients’ median number of children at diagnosis was also higher in Mexico than in Italy (1 [IQR 0-2] vs 2 [IQR 1-3], p&lt;.001). Patients’ distribution by clinical stage (p&lt;.001), timing of CT (p=.01), hormone receptor status (p=.04), and HER2 status (p=.002) also differed between cohorts: Mexican patients were more frequently diagnosed with stage III BC and received neoadjuvant CT, while Italian patients more commonly had positive hormone receptors or HER2 overexpression. Regarding fertility preservation, a technique was used in 8% and 25% of patients in Mexico and Italy, respectively (p&lt;.001). Methods comprised oocyte (50% in Mexico vs 87% in Italy), embryo (53% vs 0%; this strategy is forbidden by law in Italy), and ovarian tissue cryopreservation (0% vs 16%). GnRHa for ovarian protection were used in nearly all Italian patients (98%) but in a minority of Mexican patients (6%). Not undergoing fertility preservation was mainly due to lack of interest (47-50%), urgency to start treatment (4-6%), and personal reasons (3-5%). Fertility preservation uptake was associated with younger age (OR 1.2, 95%CI 1.1-1.2), unpartnered status (OR 3.4, 95%CI 1.9-5.9), childlessness (OR 21.8, 95%CI 10.0-47.6), private healthcare coverage in Mexico (OR 3.0, 95%CI 1.1-8.1), stage I-II BC (OR 3.1, 95%CI 1.5-6.3), positive hormone receptors (OR 2.3, 95%CI 1.2-4.6), and adjuvant CT (OR 2.4, 95%CI 1.4-4.3). Conclusions: This comparative analysis of two prospective studies in Mexico and Italy showed that a significant distinct proportion of YWBC had access to the available fertility and ovarian function preservation techniques in these countries, possibly reflecting the different social and healthcare contexts. Although all women should receive a complete oncofertility counseling, patients who are younger, unpartnered, childless, and have earlier-stage BC appear to be those who particularly benefit from being offered fertility preservation options. This study underscores the need to enhance awareness and access to oncofertility services in order to provide comprehensive, patient-centered care to this young population. Citation Format: Fernanda Mesa-Chavez, Maria Grazia Razeti, Eva Blondeaux, Alejandra Platas, Virginia Delucchi, Alan Fonseca, Valeria Fontana, Marlid Cruz-Ramos, Paola Anserini, Manuel Rolando García Garza, Edoardo Chiappe, Alejandro Mohar, Laura Orlando, Enrique Bargallo-Rocha, Saverio Cinieri, Lucia Del Mastro, Cynthia Villarreal-Garza, Matteo Lambertini. Fertility and ovarian function preservation in young women with breast cancer: A comparative analysis of two prospective cohort studies in Mexico and Italy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-03-02.

Abstract P3-02-10: Evaluation of a polygenic risk score as a predictor of breast cancer, triple-negative breast cancer, and early-onset disease in Hispanic women

2025-06-13

Holly J. Pederson , Matthew Kucera , Eudora Hu +3 more | Clinical Cancer Research

Abstract Background: Hispanic women in the U.S. have a lower incidence of breast cancer (BC) when compared to non-Hispanic white (NHW) women. However, Hispanic women diagnosed with BC tend to … Abstract Background: Hispanic women in the U.S. have a lower incidence of breast cancer (BC) when compared to non-Hispanic white (NHW) women. However, Hispanic women diagnosed with BC tend to be younger, have more advanced disease at presentation, and have a higher risk of BC mortality compared to NHW women. Some studies have suggested that these differences may be due, in part, to a higher prevalence of aggressive subtypes, including triple-negative BC (TNBC). More accurate risk prediction methods are urgently needed to identify young Hispanic women with elevated risk of BC. Incorporating polygenic risk scores (PRS) into clinical models can substantially improve risk assessment, but most PRS have demonstrated poor performance among non-European ancestries. We previously described a multiple-ancestry PRS (MA-PRS) based on 56 ancestry-informative and 329 BC-associated single-nucleotide polymorphisms (SNPs). MA-PRS predicts overall BC risk for diverse populations by characterizing genetic ancestry at each BC SNP and applying ancestry-specific SNP risks and frequencies. Here, we evaluated the extent to which MA-PRS improves upon clinical factors for the prediction of overall BC, TNBC, and early-onset (&lt; 50 years of age) disease in a large, independent cohort of self-reported Hispanic women. Methods: We examined clinical and genetic records from self-reported Hispanic women referred for hereditary cancer testing from 8/22 – 9/23 and negative for pathogenic variants in BC-associated genes. The association of MA-PRS with overall BC, TNBC and early-onset disease was analyzed using multivariable logistic regression adjusted for personal and family cancer history, age, and genetic ancestry. Analyses were conducted within the full cohort and the subpopulation of patients &lt; 50 years old. Odds ratios (OR) are reported per standard deviation (SD) with 95% confidence intervals (CI). Results: 12,384 Hispanic women met the study eligibility criteria. A total of 2,071 (16.7%) were diagnosed with BC. Of those, 876 (42.3%) were diagnosed with early-onset BC, 196 (9.5%) were diagnosed with TNBC, and 86 (4.2%) were diagnosed with early-onset TNBC. Most (59.7%) of those diagnosed with BC had no family history of breast or ovarian cancer.MA-PRS significantly improved upon clinical factors for the prediction of overall BC (OR 1.63; 95% CI 1.53-1.73), early-onset BC (OR 1.62; 95% CI 1.49-1.76), TNBC (OR 1.42; 95% CI 1.22-1.67) and early-onset TNBC (OR 1.48; 95% CI 1.18-1.86). This effect of MA-PRS on risk stratification compares favorably to the 1.4 OR per SD reported in the current literature for mammographic density, which is widely recognized as an important risk factor. Conclusions: MA-PRS substantially improved upon clinical factors for the prediction of overall BC, TNBC and early-onset disease in a large cohort of Hispanic women. Incorporation of MA-PRS into BC risk assessment has the potential to improve BC survival through more accurate identification of women at high risk. Citation Format: Holly Pederson, Matthew Kucera, Eudora Hu, Brooke Hullinger, Timothy Simmons, Elisha Hughes. Evaluation of a polygenic risk score as a predictor of breast cancer, triple-negative breast cancer, and early-onset disease in Hispanic women [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-02-10.

Abstract P3-06-15: Trajectories of Daily Step Counts in Breast Cancer Survivors in the Breast Cancer Weight Loss (BWEL) Trial

2025-06-13

Chao Cao , Karla V. Ballman , Linda McCall +7 more | Clinical Cancer Research

Abstract Background: Step count is one of the most accessible and widely used device-measured metrics for monitoring physical activity levels. Step counts are associated with hospitalizations during cancer treatment and … Abstract Background: Step count is one of the most accessible and widely used device-measured metrics for monitoring physical activity levels. Step counts are associated with hospitalizations during cancer treatment and with other health outcomes in cancer patients (pts). The BWEL (Alliance for Clinical Trials in Oncology A011401; NCT02750826) trial is a phase 3 randomized trial testing the impact of a supervised weight loss intervention (WLI) on invasive disease-free survival in 3180 women with stage II-III breast cancer (BC) and a body mass index (BMI) ≥27 kg/m2. This secondary BWEL analysis describes 2-year (yr) trajectories of daily step counts in the BWEL WLI group. Methods: Eligible pts were within 16 months (mos) of diagnosis of stage II-III HER2-negative BC, had completed chemotherapy and radiation, and were randomized 1:1 to a telephone-based WLI plus health education (HE) or an HE alone control group. WLI pts were assigned a trained coach at the BWEL call center and were provided 42 phone calls over the 2- yr intervention period. Calls were delivered weekly for the first 12 weeks (wks), biweekly for the remainder of the 1st yr, and monthly in the 2nd yr. The WLI focused on caloric restriction and exercise, with an activity goal of 150 minutes (min) of moderate to vigorous-intensity exercise per wk in the first 6 mos of WLI, increasing to 225 min/wk in mos 6-24. WLI pts were provided with a Fitbit for motivation and assessment of activity. Valid daily step counts (defined as ≥ 100 steps/day) were extracted from the BWEL portal and averaged (avg) weekly to capture habitual patterns. Linear mixed-effect models accounting for individual variances and Joinpoint regression were used to evaluate trajectories of daily step counts over the 104-wk WLI. Univariable and multivariable (including baseline age, race/ethnicity, and BMI) mixed-effect regression models were used to examine difference in daily step counts over 104 wks by pt factors. Results: Of the 1591 WLI pts, 1240 provided Fitbit data with 466,400 records of daily step counts. Pts with Fitbit data had mean baseline BMI of 34.4 (±5.6) kg/m2 and mean age of 53.2 (±10.3) yrs; 10.8% self-identified as African American (AA) and 6.1% as Hispanic. A higher proportion of individuals without Fitbit data identified as AA (19.1%) or Hispanic (10.5%) compared to those with Fitbit data (P&lt;.001). Trajectory analysis indicated that step counts increased from 4864 (95% CI: 4631-5096) to 5663 (95% CI: 5444-5882) avg steps/day from wk 1 to wk 12 (P for trend &lt;.001) and to 6647 (95% CI: 6476-6818) avg steps/day between wks 26 and 52 (both P for trend &lt;.001). Step counts decreased to 6058 (95% CI: 5782-6334) avg steps/day at wk 104 (P for trend &lt;.001) but remained significantly higher than baseline (P&lt;0.001). Patients aged ≥65 yrs had significantly lower avg daily step counts (5402 [95% CI: 5033-5772]) than those aged &lt;65 (6389 [95% CI: 6225-6552]). Avg daily step counts were also significantly lower in pts with BMI ≥35 (5503 [95% CI: 5267-5739]) vs those with BMI &lt;35 (6691 [95% CI: 6502-6879]). AA pts had lower avg daily step counts (5793 [95% CI: 5334-6252]) than pts who did not identify as AA or Hispanic (6297 [95% CI: 6128-6466]). Each 1-yr increase in age was associated with an avg 30 (95% CI: 16-44) fewer steps/day over the WLI period in a multivariable model. Similarly, each 1-unit increase in BMI was associated with 117 (95% CI: 91-143) fewer avg steps/day. Conclusions: Daily step counts significantly increased in early BC survivors during a telephone-based WLI. Further follow-up of the BWEL trial will evaluate relationships between daily step trajectories and disease and pt-reported outcomes. Support: U10CA180821, U10CA180882, UG1CA189823; U10CA180820, U10CA180863, CCS 707213, U10CA180868, UG1CA189974; https://acknowledgments.alliancefound.org. Citation Format: Chao Cao, Karla V. Ballman, Linda McCall, Thomas A. Wadden, Catherine M. Alfano, Xiaolan Feng, Linda M. Delahanty, Elizabeth Frank, Olwen Hahn, Dawn L. Hershman, Judith O. Hopkins, Melinda Irwin, Erica L. Mayer, Lori Minasian, Linda Nebeling, Marian L. Neuhouser, Electra D. Paskett, Patricia A. Spears, Vered Stearns, Cynthia A. Thomson, Anna Weiss, Julia White, Pamela J. Goodwin, Clifford Hudis, Eric P. Winer, Ann H. Partridge, Lisa A. Carey, Jennifer A. Ligibel. Trajectories of Daily Step Counts in Breast Cancer Survivors in the Breast Cancer Weight Loss (BWEL) Trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-06-15.

Abstract PS15-02: Genome-wide association study (GWAS) of aromatase inhibitor musculoskeletal toxicity (AIMT) among early-stage breast cancer (BC) survivors

2025-06-13

Pietro Lapidari , Youenn Drouet , Emilie Thomas +7 more | Clinical Cancer Research

Abstract Background: More than half of patients with early BC on aromatase inhibitors (AI) experience AIMT. Inflammatory traits linked with treatment-related estrogen depletion have been associated with AIMT. A potential … Abstract Background: More than half of patients with early BC on aromatase inhibitors (AI) experience AIMT. Inflammatory traits linked with treatment-related estrogen depletion have been associated with AIMT. A potential role for germline variants in genes regulating inflammation, bone turnover, estrogen metabolism and AI pharmacokinetics has also been suggested (Reinbolt 2018, Stearns 2024, Lintermans 2016, Wang 2016, Hertz 2017). Yet study were relatively small and results inconsistent or not validated. Therefore, the understanding of the biological and potential genetic underpinnings of AIMT is still limited. We aimed to comprehensively explore the association of genetic variants with AIMT in order to identify targets for impactful interventions. Methods: We included postmenopausal patients with stage I-III BC treated with adjuvant AI from the longitudinal CANTO cohort (NCT01993498). AIMT was evaluated at month 3-6, year (Y) 1, Y3 and Y5 of AI treatment and defined as presence of any grade [G] articular or muscular pain by CTCAE v4.0. All germline variants were assessed on blood samples obtained at BC diagnosis. We performed a GWAS between 1,894,475 single nucleotide polymorphisms (SNPs) (Illumina InfiniumExome24 / Illumina GSA24) and AIMT, using multivariable logistic regressions. Each model was adjusted on pre-specified clinical and behavioral factors, including age, socio-economic status, comorbidities, tumor and treatment-related variables (including type of AI), and patient-reported health outcomes, all assessed at BC diagnosis. Missing data was handled by multiple imputation with a set of 15 complete datasets. The study had approximately 80% power to detect associations with AIMT at Y3 at suggestive GWAS significance alpha level of 10-6 targeting variant with minor allele frequency (MAF) of 0.25 and odds ratio (OR) of 1.5. Therefore, our primary outcome of interest was AIMT at Y3. Given the exploratory nature of these analyses, we report relevant associations at an alpha threshold of 10-4. Genes harboring significant top SNPs were annotated to identify potential explicatory biological pathways. Results: Overall 4854 patients treated with AI were included. Of these, 3847 had available genetic data. Mean age was 63.9 years (SD 7.2), mean BMI was 27.0 (5.6). 63% patients reported history of articular disease, 41% received chemotherapy. 55% received letrozole, 40% anastrozole and 5% exemestane as first AI. 65% of patients reported AIMT at Y3 (of whom G3 9%), while 86% patients reported AIMT overall (at any time point; of whom G3 18%). Patients with AIMT at Y3 were generally younger, with higher BMI, had previous history of articular or muscular disease, and reported more frequently anxiety or depression at diagnosis. The GWAS identified 9 SNPs as associated with AIMT at Y3: rs4096589 (MAF 0.39; OR 1.36 [95% CI 1.21-1.53]), rs983495 (MAF 0.46; OR 0.76 [0.68-0.85]), rs12964962 (MAF 0.25; OR 0.73 [0.64-0.84]), rs348780 (MAF 0.42; OR 0.77 [0.69-0.86), rs72485589 (MAF 0.13; OR 0.67 [0.56-0.81]), rs2559854 (MAF 0.42; OR 0.78 [0.69-0.87]), rs895876 (MAF 0.16; OR 0.72 [0.61-0.83]), rs2926866 (MAF 0.17; OR 1.40 [1.20-1.66]), rs2240027 (MAF 0.08; OR 1.58 [1.28-1.96]). rs2926866 was also associated with AIMT at Y1 (1.22 [1.05-1.41]), Y5 (1.36 [1.12-1.66]), and overall (1.48 [1.24-1.76]). Relevant molecular functions that were associated with the identified SNPs included protein homodimerization activity (rs4096589), identical protein binding (rs895876), actin- and actin-filament binding (rs2240027). Conclusions: This was an exploratory study aimed to assess associations between genetic variants and AIMT in postmenopausal patients with early BC. Results of this relatively large prospective cohort identified several SNPs that might be involved in AIMT. Further analyses are warranted for model validation and to better elucidate the mechanistic role of the described genetic variants from a functional perspective. Citation Format: Pietro Lapidari, Youenn Drouet, Emilie Thomas, Jérémie Jacquemin, Maria Alice Franzoi, Martina Pagliuca, Sophie Laurent, Chayma Bousrih, Maryam Lustberg, Olivier Tredan, Anne-laure Martin, Catherine Gaudin, Christelle Jouannaud, Marion Fournier, William Jacot, Marina Rousseau, Jean Francois Deleuze, Alain Viari, Ines Vaz-Luis, Antonio Di Meglio. Genome-wide association study (GWAS) of aromatase inhibitor musculoskeletal toxicity (AIMT) among early-stage breast cancer (BC) survivors [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS15-02.

Abstract P5-10-23: The Impact of Body Mass Index on Pathological Complete Response Following Neoadjuvant Chemotherapy (NACT) in Operable Breast Cancer

2025-06-13

Richa Jaiswal , Emma Blower , Helen Innes +3 more | Clinical Cancer Research

Abstract Introduction: Breast cancer is a significant global health issue, characterized by an incidence rate of 11.7% and a mortality rate of 6.9%. Achieving a pathological complete response (PCR) after … Abstract Introduction: Breast cancer is a significant global health issue, characterized by an incidence rate of 11.7% and a mortality rate of 6.9%. Achieving a pathological complete response (PCR) after neoadjuvant chemotherapy is linked to better survival outcomes for breast cancer patients. In the United Kingdom, 63.5 % of adult population has an elevated body mass index (BMI), a figure that has been rising over time.Objective: The objective of this study was to find out whether the body mass index of breast cancer patients had any impact on pathological response following neoadjuvant chemotherapy, and, if so, to compare the rate of achieving complete pathological response between normal body mass index (18- 24.9) and those with an elevated body mass index (≥25).Material and Methods: The study included all the female with biopsy-confirmed operable breast carcinoma who underwent surgery after receiving neoadjuvant chemotherapy between January 2018 and December 2022. Patients were categorized into two BMI groups: normal (18-24.9) and elevated (≥25). Pathological complete response was defined as ypT0/Tis ypN0, ypT0/Tis, or ypN0. Descriptive analyses were performed. Univariate and multivariate logistic regression analyses were conductedusing R software.Results: A total of 829 breast cancer patients were included in the study. Of these, 277(33.31%) had a normal BMI and 552(66.59%) had an elevated BMI. Patients with a normal BMI had the highest rate of pathological complete response (68.23%), whereas those with an elevated BMI had a lower PCR rate (32.43%) (p&lt;0.001). Body mass index remained an independent predictor of pathological complete response (OR=1 for normal BMI and OR=0.21for elevated BMI; p&lt;0.001).Conclusion: In this cohort, breast cancer patients with an elevated body mass index had a lower rate of pathological complete response following neoadjuvant chemotherapy. Further studies are needed to elucidate the underlying mechanisms. Citation Format: Richa Jaiswal, Emma Blower, Helen Innes, Raj Sripadam, Petros Yiannoullou, Leena Chagla. The Impact of Body Mass Index on Pathological Complete Response Following Neoadjuvant Chemotherapy (NACT) in Operable Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-10-23.