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Associations of sex steroid hormones with mortality in women with breast cancer

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Abstract

Epidemiological studies have demonstrated associations between circulating levels of sex steroid hormones and risk of breast cancer in postmenopausal women. However, data on associations with breast cancer survival are limited. We measured levels of estradiol, estrone, testosterone, and sex hormone-binding globulin (SHBG), in serum collected on average 30 months after diagnosis from 358 postmenopausal women diagnosed with stage I-IIIA breast cancer between 1995 and 1998 who participated in a multiethnic, prospective cohort study. Women were followed through December, 2012. We evaluated associations between log-transformed analytes and breast cancer-specific and all-cause mortality fitting multivariable Cox proportional hazards models. Over a median of 14.5 years of follow-up, 102 deaths occurred; 43 of these were due to breast cancer. In models adjusted for ethnicity/study site, age, body mass index, and tumor stage, increased levels of log-transformed SHBG were associated with reduced risk of both breast cancer-specific mortality (hazard ratio, HR 0.48; 95 % confidence interval, CI 0.26–0.89) and all-cause mortality (HR 0.64, 95 % CI 0.43–0.97). There were no associations between levels of estradiol, estrone, or testosterone for either endpoint. In subgroup analyses, after correction for multiple testing, increased estrone was significantly associated with reduced risk for breast cancer-specific mortality among participants with ER-negative tumors (HR 0.16, 95 % CI 0.05–0.63) but not among participants with ER-positive tumors. Increased serum levels of SHBG were associated with decreased risk of breast cancer-specific and all-cause mortality in women with breast cancer. These results should be confirmed in larger breast cancer survivor cohorts.

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Abbreviations

SHBG:

Sex steroid hormone-binding globulin

ER:

Estrogen receptor

PR:

Progesterone receptor

HEAL:

Health, eating, activity, and lifestyle study

SEER:

Surveillance, epidemiology, and end results

HR:

Hazard ratio

HRT:

Hormone replacement therapy

CI:

Confidence interval

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Acknowledgments

We would like to thank the HEAL participants for their dedication to this study

Funding

National Cancer Institute (N01-CN-75036-20, N01-CN-05228, N01-PC-67010, U54-CA116847, U54CA116848, R25-CA94880); National Institutes of Health (M01-RR-00037); University of New Mexico (NCRR M01-RR-0997); National Institute of Child Health and Human Development (N01-HD-3-3175); California Department of Health Services (050Q-8709-S1528).

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Correspondence to Catherine Duggan.

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The authors declare that they have no conflict of interest.

Ethical Statement

This study was performed with the approval of the Institutional Review Boards of participating centers in accordance with assurances filed with and approved by the U.S. Department of Health and Human Services.

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Duggan, C., Stanczyk, F., Campbell, K. et al. Associations of sex steroid hormones with mortality in women with breast cancer. Breast Cancer Res Treat 155, 559–567 (2016). https://doi.org/10.1007/s10549-016-3704-4

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  • DOI: https://doi.org/10.1007/s10549-016-3704-4

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