Postmenopausal levels of sex hormones and risk of breast carcinoma in situ: Results of a prospective study

We report on a prospective study to assess the association of postmenopausal serum levels of sex hormones with subsequent risk of breast carcinoma in situ. We conducted a case-control study nested within the cohort of the New York University Women's Health Study, a large prospective study documenting a positive association of circulating levels of estrogens and androgens with invasive breast cancer. The study included 69 cases of incident in situ carcinoma and 134 individually matched controls. No statistically significant trend of increasing risk with increasing level of any of the hormones was observed. Odds ratios (95% CIs) for the highest tertile relative to the lowest were 1.10 (0.51-2.39) for estradiol, 0.95 (0.41-2.19) for estrone, 1.63 (0.69-3.88) for testosterone, 0.99 (0.44-2.24) for androstenedione, 0.99 (0.45-2.20) for dehydroepiandrosterone sulfate and 0.81 (0.38-1.74) for sex hormone-binding globulin. Adjusting for potential confounders did not materially affect the results, nor did limiting the analysis to the 59 cases of ductal carcinoma in situ, the lesion thought to be the direct precursor of most invasive breast cancers. Our results are at variance with the positive associations observed in this same cohort with risk of invasive breast cancer. Possible explanations for our results include lack of power, an effect of sex hormones limited to the progression from in situ to invasive tumors, over-representation of indolent tumors or an effect of sex hormones on the induction of only a subset of in situ tumors, those that would develop into invasive tumors. (C) 2004 Wiley-Liss, Inc.