Abstract LB-275: Adult body size and physical activity in relation to risk of breast cancer defined by tumor androgen receptor status
Authors: Zhang Xuehong , Eliassen A. Heather , Tamimi Rulla , Hazra Aditi , Beck Andrew H. , Brown Myles , Collins Laura C. , Rosner Bernard , Hankinson Susan E. 
Published: May 2015

Abstract
Background: In contrast to the well-established role of estrogens in breast cancer risk and survival, the role of androgens in breast carcinogenesis is unclear. Previous studies have shown that, in postmenopausal women, higher body mass index (BMI) and being less physically active are associated with an increased risk of invasive breast cancer, and the associations generally are stronger for estrogen receptor (ER) and/or progesterone receptor (PR) positive tumors. Although the androgen pathway also may play a mechanistic role with these breast cancer risk factors, no prior studies have specifically evaluated these associations by tumor androgen receptor (AR) status. Observing differential associations by AR status would provide etiologic insights into the contribution of the androgen pathway in breast carcinogenesis.
Methods: We evaluated the associations of adult body size and physical activity with risk of incident invasive breast cancer by AR status in the Nurses’ Health Study. We used validated questionnaires to assess height, weight, and physical activity. AR status was determined using immunohistochemistry on sections from tumor tissue microarrays (TMAs); ER and PR status were determined using TMAs or medical record pathology reports. We applied a constrained competing risk survival model to evaluate these associations by AR status while controlling for ER/PR status and established breast cancer risk factors.
Results: A total of 2,198 cases (1,701 AR+; 497 AR- tumors) were documented during 26 years of follow-up of 96,966 eligible women. After adjusting for ER/PR status and other breast cancer risk factors, higher BMI was associated with an increased risk of both AR+ and AR- tumors. The multivariable hazard ratios (MV HRs) and 95% confidence intervals (95%CIs) for every 5 kg/m2 increase in BMI were 1.05 (0.99, 1.10) for AR+ and 1.10 (1.00, 1.22) for AR- tumors (p-value for heterogeneity=0.46). Further, women engaged in higher amounts of total physical activity including brisk walking were at a lower risk of developing breast cancer. The MV HRs (95%CIs) per approximately 5 hours of brisk walking per week were 0.87 (0.72, 1.05) for AR+ and 0.69 (0.46, 1.04) for AR- tumors (p-value for heterogeneity=0.32). We further examined these associations by the combinations of ER/PR/AR status and observed that only BMI associations differed significantly across these subtypes (p-value for heterogeneity=0.03). The MV HRs (95%CIs) for 5 kg/m2 increase in BMI were 1.15 (1.08, 1.23) for ER+PR+AR+, 1.23 (1.04, 1.45) for ER+PR+AR-, 0.88 (0.75, 1.03) for ER+PR-AR+, 1.08 (0.92, 1.28) for ER-PR-AR+, 1.19 (1.01, 1.39) for ER-PR-AR-, 0.92 (0.70,1.22) for ER+PR-AR-.
Conclusion: In postmenopausal women, higher adult body size was associated with an increased risk of both AR+ and AR- tumors while physical activity, including brisk walking, was associated with a reduced risk of both subtypes. The strongest associations observed with the ER+PR+AR- and ER+PR+AR+ tumors (i.e., subtypes with the most active estrogen signaling) supports the important role of estrogen signaling in the postmenopausal BMI/breast cancer relationship. Further, the positive association observed between BMI and ER-PR-AR- tumors suggests pathways other than sex steroids (e.g., the insulin pathway) also might play an etiologic role and more studies are warranted to confirm and extend these findings.
Citation Format: Xuehong Zhang, A. Heather Eliassen, Rulla Tamimi, Aditi Hazra, Andrew H. Beck, Myles Brown, Laura C. Collins, Bernard Rosner, Susan E. Hankinson. Adult body size and physical activity in relation to risk of breast cancer defined by tumor androgen receptor status. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-275. doi:10.1158/1538-7445.AM2014-LB-275