AS167 - Sex hormones, risk factors, and risk of ER+ and ER- breast cancer

Investigator Names and Contact Information

Steve Cummings (scummings@sfcc-cpmc.net)

Introduction/Intent

SERMS substantially reduce ER+ but not ER- breast cancer risk. Estradiol and testosterone levels may be much stronger than risk factors as predictors of ER+ cancer and, therefore, useful to identify women who would benefit from chemoprevention. Additionally, there have been no adequately powered studies of sex hormones and risk of ER- breast cancer.

Those postmenopausal women with the highest concentrations of testosterone and estradiol will have the highest risk of ER+ but not ER- breast cancer. We will measure plasma estradiol and testosterone levels in 200 invasive ER+ and 200 invasive ER- breast cancer incident cases and 600 randomly selected controls, providing a power of 0.90 to detect a 1.3-fold increased risk of ER+ or ER- breast cancer per S.D. increase in hormone level. We have coordinated our proposed measurements with other WHI-OS breast cancer studies and would use plasma instead of the scarcer serum resource. A positive result would suggest that it is worthwhile to measure sex hormones in postmenopausal women to identify those most likely to benefit from chemoprevention of breast cancer.

Our goal is to better identify women who are at increased risk for breast cancer and who may benefit most from preventive therapies. In particular, we propose that circulating sex hormone measurements may serve to better identify older women who are at increased risk for estrogen receptor positive (ER+) breast cancer and for whom prevention such as with selective estrogen receptor modulators (SERMs) may be particularly beneficial. We propose to use data and stored specimens from the WHI-OS in a nested case-control study to test the following hypotheses:

1. High circulating concentrations of estradiol or testosterone are associated with an increased risk of invasive ER+ breast cancer.

2. High circulating concentrations of estradiol or testosterone are not significantly associated with an increased risk of ER- breast cancer.

• a. The association between circulating estradiol level and testosterone level and risk of cancer is significantly stronger for ER+ than ER- breast cancer.

3. Putative reproductive risk factors for breast cancer will not be significantly associated with risk of ER+ nor ER- among the postmenopausal women in WHI. It will allow us to compare strength of risk factors and sex hormone levels.

Results/Findings

Some of the publications related to this ancillary study are:

Ms622 - Farhat GN, Cummings SR, Chlebowski RT, Parimi N, Cauley JA, Rohan TE, Huang AJ, Vitolins M, Hubbell FA, Manson JE, Cochrane BB, Lane DS, Lee JS. Sex hormone levels and risks of estrogen receptor-negative and estrogen receptor-positive breast cancers. J Natl Cancer Inst. 2011 Feb 17. [Epub ahead of print]

Ms1173 - Hvidtfeldt UA, Gunter MJ, Lange T, Chlebowski RT, Lane DS, Farhat GN, Freiberg MS, Keiding N, Lee JS, Prentice R, Tjonneland A, Vitolins MZ, Wassertheil-Smoller S, Strickler HD, Rod NH. Quantifying mediating effects of endogenous estrogen and insulin in the relation between obesity, alcohol consumption and breast cancer. Cancer Epidemiol Biomarkers Prev. 2012 May 7. [Epub ahead of print] For a complete, up-to-date list of WHI papers related to this ancillary study, please use the searchable Bibliography section of this website. To search for papers by study number, access the Simple Search, and enter the study number in the “Related Studies” field.