Breast Cancer Research and Treatment

, Volume 155, Issue 3, pp 559–567 | Cite as

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

  • Catherine DugganEmail author
  • Frank Stanczyk
  • Kristin Campbell
  • Marian L. Neuhouser
  • Richard N. Baumgartner
  • Kathy B. Baumgartner
  • Leslie Bernstein
  • Rachel Ballard
  • Anne McTiernan


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.


Breast cancer Mortality Sex steroid hormones 



Sex steroid hormone-binding globulin


Estrogen receptor


Progesterone receptor


Health, eating, activity, and lifestyle study


Surveillance, epidemiology, and end results


Hazard ratio


Hormone replacement therapy


Confidence interval



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


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).

Compliance with ethical standards

Conflict of Interest Statement

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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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Catherine Duggan
    • 1
    Email author
  • Frank Stanczyk
    • 2
  • Kristin Campbell
    • 3
  • Marian L. Neuhouser
    • 1
  • Richard N. Baumgartner
    • 4
  • Kathy B. Baumgartner
    • 4
  • Leslie Bernstein
    • 5
  • Rachel Ballard
    • 6
  • Anne McTiernan
    • 1
    • 7
  1. 1.Division of Public Health SciencesFred Hutchinson Cancer Research CenterSeattleUSA
  2. 2.Department of Obstetrics, Gynecology, and Preventive Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  3. 3.Faculty of MedicineUniversity of British ColumbiaVancouverCanada
  4. 4.Department of Epidemiology and Population Health, School of Public Health and Information Sciences, James Graham Brown Cancer CenterUniversity of LouisvilleLouisvilleUSA
  5. 5.Department of Population Sciences, Division of Cancer EtiologyBeckman Research Institute of the City of HopeDuarteUSA
  6. 6.Office of Disease PreventionNational Institutes of HealthBethesdaUSA
  7. 7.University of Washington Schools of Public Health and MedicineSeattleUSA

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