Abstract 5286: Type 2 diabetes and increased risk of estrogen receptor-negative breast cancer in African American women

Introduction: Type 2 diabetes (T2D) is hypothesized to be a risk factor for breast cancer. Possible mechanisms include adverse effects of impaired glucose regulation on endogenous hormone levels and increased inflammation of adipose tissue, which may be favorable to breast epithelial cell transformation, tumor-related angiogenesis, and cancer cell invasion. Recent meta-analyses suggest that T2D may be associated with a 15-20% increase in risk, but whether that increase is due to residual confounding by body mass index (BMI) is uncertain. Further, few studies have reported results separately by estrogen receptor (ER) status of the tumor, none have had appreciable numbers of ER- cases, and the only previous report on the association in African American (AA) women analyzed all subtypes together. Methods: We used data from the prospective Black Women’s Health Study to examine the relation of T2D to incidence of invasive breast cancer, overall and by ER subtype, among 54,337 AA women free from T2D and breast cancer at baseline and followed for 20 years. Included were 1,851 incident breast cancer cases, with 468 classified as ER- and 914 as ER+; data on ER status were not available for 469 cases. Participants were asked about medical conditions on each biennial questionnaire. In a validation study, 95% of self-reports of diabetes were confirmed by medical records. Cox proportional hazards regression was used to compute incidence rate ratios (IRR) for breast cancer for women with T2D relative to women without T2D, controlling for age, family history of breast cancer, BMI at age 18, waist-hip ratio, years of education, and reproductive factors. Results: The multivariable IRR for T2D versus no diabetes was 1.20 (95% confidence interval 1.01-1.41) for all breast cancer, 1.42 (1.02-1.98) for ER- breast cancer, and 1.06 (0.83-1.36) for ER+ breast cancer. Most cases had had diabetes for at least five years before the breast cancer diagnosis. IRRs for ≥5 years duration of diabetes were 1.46 (1.02-2.07) for ER- and 1.08 (0.83-1.41) for ER+ breast cancer. Recent BMI was not associated with increased risk of either ER subtype and was not a confounder in the present analyses. BMI at age 18, which was inversely associated with breast cancer risk in this and other studies, was the only appreciable confounder; in multivariable models that did not control for BMI at age 18, IRRs were 1.37 (0.99-1.90) and 1.03 (0.81-1.33) for ER- and ER+ breast cancer, respectively. Conclusions: The findings suggest that AA women with T2D are at increased risk of ER- breast cancer. AA women are about two times as likely to be diagnosed with ER- breast cancer as are U.S. white women and also have a markedly higher prevalence of T2D. Their higher prevalence of diabetes may contribute to the disparity in incidence of ER- breast cancer. The next step will be to assess whether risk of ER- breast cancer among diabetic women differs according to how well the diabetes is controlled. Citation Format: Julie R. Palmer, Nelsy Castro-Webb, Kimberly A. Bertrand, Traci N. Bethea, Lynn Rosenberg. Type 2 diabetes and increased risk of estrogen receptor-negative breast cancer in African American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5286. doi:10.1158/1538-7445.AM2017-5286