Abstract
Prospective studies have shown an association between increased serum levels of estradiol and testosterone and breast cancer risk in postmenopausal women. Raloxifene has been shown to reduce breast cancer risk more in women with high estradiol levels than in those with lower levels. The purpose of this study was to determine whether sex hormone levels were associated with breast cancer risk and with response to tamoxifen in a high-risk population. Using a case-cohort design, we studied 135 women with postmenopausal breast cancer and 275 postmenopausal women without breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project Cancer Prevention Trial (P-1) and who had been treated with tamoxifen or placebo for 69 months. We measured estradiol, testosterone, and sex hormone-binding globulin by using radioimmunoassay in baseline plasma samples. Relative risks (RRs) and 95% confidence intervals (CIs) for invasive breast cancer were estimated for each quartile of sex hormone level using Cox proportional hazards models. All statistical tests were two-sided. Median plasma levels of estradiol, testosterone, and sex hormone-binding globulin were similar between the case and cohort groups. The relative risk of breast cancer for women in the placebo group was not associated with sex hormone levels (risk of estrogen receptor-positive breast cancer in women by quartile of estradiol: Q1 [lowest], RR = 1.0; Q2, RR = 1.16, 95% CI = 0.49 to 2.7; Q3, RR = 1.08, 95% CI = 0.45 to 2.61; and Q4, RR = 1.29, 95% CI = 0.59 to 2.82). The reduced risk of invasive breast cancer in tamoxifen-treated women compared with placebo-treated women was not associated with sex hormone levels. These data do not support the use of endogenous sex hormone levels to identify women who are at particularly high risk of breast cancer and who are most likely to benefit from chemoprevention with tamoxifen.
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