Sex hormone levels and breast cancer risk

Although prior studies have shown an association with higher levels of serum estradiol and testosterone with breast cancer in post-menopausal women, our study of high risk women enrolled in the Breast Cancer Prevention Trial (P-1) showed no association.  This was the first study to examine this association in "high risk" women, as most prior studies involved cohort populations with risks similar to those of the general population.  The P-1 population was unique, in that they had very careful assessment of breast cancer risk using the Gail score.  In order to enroll in the P-1 trail, women had to have a 5 year risk of developing breast cancer of at least 1.7%.  
Because P-1 was a randomized controlled trial of tamoxifen, we were also able to examine whether tamoxifen showed any increased efficacy in women with high levels of estradiol and/or testosterone.  Overall, P-1 showed that tamoxifen reduced the risk of breast cancer by about 50%.  In this sub-study of P-1, tamoxifen was effective for reducing ER+ breast cancer, regardless of estradiol or testosterone level.  
These results were somewhat surprising, as the Multiple Outcomes of Raloxifene (MORE) study showed both an association of estradiol with breast cancer risk and an increased efficacy of raloxifene for women with the highest levels of estradiol.  MORE, however, examined osteoporotic women, who are not at high risk of breast cancer.  In P-1, many women had strong family histories and possibly ongoing breast disease, as evidenced by atypia.  So, with these risk factors, sex hormone levels may not be as predictive.  Future studies will need to examine the association of estradiol and testosterone with breast cancer risk in other high risk populations.

Bibliograhical reference:

Beattie MS et al.: "Endogenous sex hormones, breast cancer risk, and tamoxifen response: an ancillary study in the NSABP Breast Cancer Prevention Trial (P-1)", J Natl Cancer Inst. 2006 Jan 18;98(2):110-5
 

Mary S. Beattie
Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, CA