Pre-diagnostic sex hormone levels and survival among breast cancer patients
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Higher levels of circulating sex steroid hormones are associated with increased breast cancer risk, though their association with prognosis remains unclear. We evaluated the association between circulating sex hormone levels and breast cancer survival in two large cohorts.
We evaluated this association among 2073 breast cancer cases from the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII) cohorts. Women in this analysis provided a blood sample in 1989–1990 (NHS) or in 1996–1999 (NHSII) and were subsequently diagnosed with breast cancer. Levels of estradiol (postmenopausal women only), testosterone, dehydroepiandrosterone-sulfate (DHEAS), and sex hormone-binding globulin (SHBG) were measured in plasma. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for survival, adjusting for patient and tumor characteristics.
A total of 639 deaths and 160 breast cancer deaths occurred over follow-up through 2015. Compared to women in the lowest quartile, postmenopausal women in the highest quartile of estradiol experienced a 1.43-fold overall mortality rate (HR 1.43, 95% CI 1.03–1.97, P-trend = 0.04) and a nonsignificantly higher breast cancer mortality rate (HR 1.50, 95% CI 0.75–2.98, P-trend = 0.12). Higher DHEAS levels were nonsignificantly associated with better overall survival (HRQ4vsQ1=0.79, 95% CI 0.57–1.10, P-trend = 0.05), though not with breast cancer survival. No associations were observed between testosterone or SHBG and survival.
Pre-diagnostic postmenopausal circulating estradiol levels were modestly associated with worse survival among breast cancer patients. Further studies should evaluate whether circulating hormone levels at diagnosis predict cancer prognosis or treatment response.
KeywordsBreast cancer Prognosis Estradiol Testosterone DHEAS SHBG
We would like to thank the participants and staff of the Nurses’ Health Study and Nurses’ Health Study II for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data.
This work was supported by the National Cancer Institute at the National Institute of Health (P50CA168504, UM1CA186107, UM1CA176726, P01CA87969, R01CA49449, R01CA67262). KHK was supported through National Research Service Awards F31CA192462 and T32CA009001 by the National Cancer Institute. MB is supported by the Breast Cancer Research Foundation. The study sponsors had no role in the design of the study; the collection, analysis, and interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication.
Compliance with ethical standards
Conflict of interest
MB receives sponsored research support from and has been a consultant to Novartis. MB has served on the scientific advisory board of Gtx, Inc. and currently serves on the scientific advisory board of Kronos Bio. The remaining authors declare they have no conflict of interest.
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