Abstract
Sex steroid hormones contribute to breast cancer development, but data on concentrations of these within breast tissue are limited. We performed simultaneous multiparameter measurement of breast sex steroids, breast epithelial cytology, and DNA methylation in 119 healthy women (54 pre- and 65 postmenopausal) without a history of breast cancer. Random fine-needle aspiration (rFNA) of the breast was performed simultaneously with blood collection. Breast samples were analyzed by LC/MS-MS for estrone, estradiol, progesterone, androstenedione, and testosterone. Blood samples were assayed for estradiol and progesterone by immunoassay. Cytomorphology was classified using the Masood Score, and DNA methylation of eight genes was analyzed using quantitative multiplexed methylation-specific PCR, and expressed as the cumulative methylation index (CMI). Serum and breast concentrations of estradiol and progesterone showed significant correlation (Spearman r = 0.34, Padj = 0.001 and r = 0.69, Padj < 0.0006, respectively). Progesterone concentration was significantly higher in the premenopausal breast (Padj < 0.0008), and showed a luteal surge. Breast estrone and estradiol concentrations did not differ significantly by menopause, but androstenedione concentration was higher in the breasts of postmenopausal women (P = 0.026 and Padj = 0.208). Breast androgens were significantly correlated with breast density (Spearman r = 0.27, Padj = 0.02 for testosterone) and CMI (Spearman r = 0.3, Padj = 0.038 for androstenedione). Our data indicate that future larger studies of breast steroid hormones along with other parameters are feasible. Significant associations of breast androgen concentrations with breast density and gene methylation warrant future study. Cancer Prev Res; 11(9); 557-68. ©2018 AACR.
Highlights
Lifetime sex steroid exposure is a determinant of breast cancer risk, as evidenced by a wealth of epidemiologic data [1, 2]
Of significant interest is the influence of local hormone concentration on the DNA methylation status of cancer-related genes, a potentially powerful risk indicator for breast cancer [23,24,25], which we have previously shown to be related to cytologic atypia [26, 27]
We report on sex steroid hormone concentrations within breast tissue, its physiologic variation in a subset of 119 women, and explore relations of breast hormones with cytology, DNA methylation, and established clinical risk factors
Summary
Lifetime sex steroid exposure is a determinant of breast cancer risk, as evidenced by a wealth of epidemiologic data [1, 2]. Direct measurement of systemic hormone exposure has been performed in multiple studies, which show that elevated concentration of serum estrogens and androgens are related to higher breast cancer risk among postmenopausal women [3,4,5]. Local synthesis of estradiol has been directly demonstrated in the breast from circulating androgens and estrone sulfate [6,7,8,9], and is implicated as part of the mechanism for obesity-associated breast cancer [10, 11]. Note: Supplementary data for this article are available at Cancer Prevention Research Online (http://cancerprevres.aacrjournals.org/).
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