Plasma sex hormone concentrations and subsequent risk of breast cancer among women using postmenopausal hormones.

BACKGROUND Sex hormone concentrations are associated with breast cancer risk among women not using postmenopausal hormones (PMH); however, whether a relationship exists among PMH users is unknown. Therefore, we conducted a prospective, nested case-control study within the Nurses' Health Study (NHS) cohort to examine the association between plasma sex hormone concentrations and postmenopausal breast cancer among women using PMH at blood collection. METHODS Blood samples were collected from 1989 to 1990. During follow-up through May 31, 2000, 446 women developed breast cancer and were matched by age, date and time of day of blood collection, and fasting status to 459 control subjects (PMH users) who did not develop cancer. We used conditional logistic regression to estimate relative risks (RRs) and 95% confidence intervals (CIs). We compared hormone concentrations of the 459 control subjects with those of 363 postmenopausal NHS participants not taking PMH. All statistical tests were two-sided. RESULTS PMH users had statistically significantly higher estradiol, free estradiol, sex hormone-binding globulin, and testosterone, and lower free testosterone concentrations than non-PMH users. Among PMH users, we found modest associations with breast cancer risk when comparing the highest versus lowest quartiles of free estradiol (RR = 1.7, 95% CI = 1.1 to 2.7; P(trend) = .06), free testosterone (RR = 1.6, 95% CI = 1.1 to 2.4; P(trend) = .03), and sex hormone-binding globulin (RR = 0.7, 95% CI = 0.5 to 1.1; P(trend) = .04), but not of estradiol or of testosterone. However, estradiol and free estradiol were statistically significantly positively associated with breast cancer risk among women older than 60 years (RR = 2.8, 95% CI = 1.5 to 5.0; P(trend) = .002 and 2.6, 95% CI = 1.4 to 4.7; P(trend) = .001, respectively) and among women with a body mass index of less than 25 kg/m2 (RR = 1.8, 95% CI = 1.1 to 3.1, P(trend) = .01 and 2.4, 95% CI = 1.4 to 4.0, P(trend) = .003, respectively). CONCLUSION Although women using PMH have a different hormonal profile than those not using PMH, plasma sex hormone concentrations appear to be associated with breast cancer risk among PMH users.