Breast Cancer Research and Treatment

, Volume 137, Issue 3, pp 883–892 | Cite as

Postmenopausal plasma sex hormone levels and breast cancer risk over 20 years of follow-up

  • Xuehong Zhang
  • Shelley S. Tworoger
  • A. Heather Eliassen
  • Susan E. Hankinson


Plasma estrogen and androgen levels are positively associated with postmenopausal breast cancer risk, but how long a single blood measurement can predict risk and whether the associations vary by tumor hormone receptor status remain unclear. We conducted nested case–control analyses within the Nurses’ Health Study. Blood samples were collected in 1989–1990 and again in 2000–2002. Among postmenopausal women not using postmenopausal hormones at blood collection, 707 cases were diagnosed through June 2010, with two matched controls per case. We used unconditional logistic regression analyses to estimate the relative risks controlling for other breast cancer risk factors. The intra-class correlation coefficients for two blood measurements collected 10 years apart ranged from 0.54 (dehydroepiandrosterone sulfate, DHEAS) to 0.74 (sex hormone-binding globulin, SHBG). Overall, women in the top (vs. bottom) 25 % of levels of estradiol, free estradiol, testosterone, free testosterone, and DHEAS were at a 50–110 % higher risk of breast cancer (p trend < 0.001). SHBG was inversely associated with risk (p trend = 0.004). RRs were similar when comparing cases diagnosed 1–10 versus 11–20 years (or 16–20 years) after blood collection (p interaction > 0.2). Except for DHEAS, the associations varied significantly by hormone receptor status (p heterogeneity ≤ 0.02). For example, the RRs (95 % CIs) comparing the highest versus lowest quartile were 2.8 (2.0–4.0; p trend < 0.001) for ER +/PR + tumors versus 1.1 (0.6–2.1; p trend = 0.98) for ER−/PR− tumors for estradiol, and 1.8 (1.3–2.5; p trend < 0.001) versus 0.6 (0.3–1.2; p trend = 0.35) for testosterone. One measure of circulating sex hormones in postmenopausal women can predict risk of hormone receptor positive breast cancer for up to 16–20 years.


Breast cancer Estrogens Androgens Hormone receptor 



This work was supported by the National Institute of Health grants CA49449 and CA87969. We appreciate the participants and staff of the Nurses’ Health Study 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.

Conflict of interest

The authors declare that they have no conflict of interest. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

Ethical standards

The experiments comply with the current laws of the country in which they were performed.

Supplementary material

10549_2012_2391_MOESM1_ESM.docx (37 kb)
Supplementary material 1 (DOCX 37 kb)


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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Xuehong Zhang
    • 1
    • 4
  • Shelley S. Tworoger
    • 1
    • 2
  • A. Heather Eliassen
    • 1
    • 2
  • Susan E. Hankinson
    • 1
    • 2
    • 3
  1. 1.Channing Division of Network Medicine, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  2. 2.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  3. 3.Division of Biostatistics and EpidemiologySchool of Public Health and Health Sciences, University of MassachusettsAmherstUSA
  4. 4.Channing Laboratory at Landmark Center (West Wing)Brigham and Women’s Hospital and Harvard Medical SchoolBostonUSA

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