W10 - Sex Hormones and Related Biomarkers as Breast Cancer Risk in the WHI Hormones Therapy Trials

This page provides study documentation for Core Study W10. For description of the specimen results, see Specimen Results Description (open to public). Data sets of the specimen results are included in the existing WHI datasets located on the WHI Data on this site (sign in and a completed Data Distribution Agreement are required; see details on the Data site.

Investigator Names and Contact Information

Core study approved by WHI Steering Committee


Several studies(#1-7) have examined the relationship between breast cancer risk and endogenous sex hormones among postmenopausal women not using hormone therapy.  Most support an association between breast cancer and estrogens, testosterone, and SHBG as individual markers of risk.  There are currently no published studies examining whether hormone therapy effects on breast cancer risk are modified by endogenous hormone levels.  Further, it is of interest to know whether the observed effects of E+P and E-alone on breast cancer risk are at least in part mediated through changes in circulating levels.
The primary objectives of this project are:
1)    To explore the extent to which the effects of HT on breast cancer risk are modified by baseline circulating levels of sex hormones and sex hormone binding globulin (SHBG) [hereafter referred to as sex hormones].
2)    To determine to what extent the changes in circulating levels of sex hormones explain the difference in breast cancer risk associated with E+P and E-Alone.
To address these broad aims we propose to measure a panel of sex hormone levels at baseline and year 1 in a nested case-control study in both HT trials.   
1.  Toniolo PG, Levitz M, Zeleniuch-Jacquotte A, et al. A prospective study of endogenous estrogens and breast cancer in postmenopausal women. J Natl Cancer Inst. 1995; 87: 190-197.
2.  Dorgan JF, Longcope C, Stephenson HE Jr., et al. Relation of prediagnostic serum estrogen and androgen levels to breast cancer risk. Cancer Epidemiol Biomarkers Prev. 1996; 5: 533-539.
3.  Cauley JA, Lucas FL, Kuller LH, Stone K, Browner WS, Cummings SR. Elevated Serum Estradiol and Testosterone Concentrations are Associated with a High Risk for Breast Cancer. Ann Intern Med. 1999; 130: 270-277.
4.  Hankinson SE, Willett WC, Manson JE, et al. Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 1998; 90: 1292-1299.
5.  Missmer SA, Eliassen H, Barbieri RL, Hankinson SE. Endogenous estrogen, androgen and progesterone concentrations and breast cancer risk among postmenopausal women. JNCI 2004;96:1856-65.
6. Zeleniuch-Jacquotte A, Shore RE, Koenig KL, et al. Postmenopausal levels of oestrogen, androgen and SHBG and breast cancer: long-term results of a prospective study. British J of Cancer (2004) 90:153-9.
7. The Endogenous Hormones, Breast Cancer Collaborative Group, Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies, J. Natl. Cancer Inst. 94 (2002), pp. 606–616.