Abstract 2257: Pre-diagnostic sex hormone levels and breast cancer survival in the Nurses' Health Study
Authors: Kensler Kevin H. , Eliassen A. Heather , Rosner Bernard A. , Hankinson Susan E. , Brown Myles , Tamimi Rulla M. 
Published: July 2017

Abstract
Background The role of estrogens has been well established in the development and progression of breast cancers, while an independent function of androgens remains to be fully elucidated. There is consistent evidence that increased levels of circulating sex steroid hormones predict subsequent breast cancer risk. However, few studies to date have evaluated circulating sex hormone levels in relation to breast cancer prognosis and the limited available evidence suggests that higher estrogen and androgen levels are associated with worse prognosis. Identifying the distinct roles of estrogens and androgens and their hormone receptor signaling pathways in breast cancers may inform novel approaches to breast cancer prevention and treatment.
Methods We evaluated the association between pre-diagnostic circulating sex hormones and breast cancer survival among 683 breast cancer cases from the Nurses’ Health Study (NHS) cohort. The NHS began in 1976 with the enrollment of U.S. registered nurses between the ages of 30 and 55. The women in this analysis provided a blood sample in 1989-1990, were postmenopausal and not using menopausal hormone therapy at the time of blood draw, and were diagnosed with invasive breast cancer between 1990 and 2010. Levels of estradiol, estrone, estrone sulfate, testosterone, androstenedione, DHEA, DHEAS, and SHBG were measured in plasma. The association between hormone levels and survival was assessed through construction of Kaplan-Meier survival curves and through use of Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals adjusted for patient, tumor, and treatment covariates.
Results Over follow-up through 2014, a total of 219 deaths occurred, including 57 breast cancer deaths. For each hormone, we found no association with breast cancer survival by the log-rank test. Upon adjustment for patient, tumor, and treatment covariates, we observed non-significant 47% increases in breast cancer mortality per unit increase in log estradiol (HR=1.47, 95% CI 0.94-2.31) and estrone sulfate (HR=1.47, 95% CI 0.97-2.24). Log testosterone was not associated with breast cancer survival (HR=0.84, 95% CI 0.46-1.53) and the findings were null for the other hormones. These findings were robust when evaluating overall survival and when stratifying by tumor estrogen receptor expression.
Conclusions We observed no significant associations between pre-diagnostic sex hormone levels and breast cancer survival among postmenopausal women. This is the first analysis to evaluate pre-diagnostic hormone levels in relation to survival. Though limited by sample size, it improves upon past analyses of post-diagnostic hormone levels by reducing the possibility of the tumor affecting hormone levels and by better accounting for tumor and treatment characteristics. The findings should be replicated in a larger population to further assess the prognostic value of circulating sex hormones in breast cancer survival.
Citation Format: Kevin H. Kensler, A. Heather Eliassen, Bernard A. Rosner, Susan E. Hankinson, Myles Brown, Rulla M. Tamimi. Pre-diagnostic sex hormone levels and breast cancer survival in the Nurses' Health Study [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 2257. doi:10.1158/1538-7445.AM2017-2257