Circulating estrogens and estrogens within the breast among postmenopausal BRCA1/2 mutation carriers

• Published in: Breast cancer research and treatment Vol. 143; no. 3; pp. 517 - 529
• Main Authors: Loud, Jennifer T., Gierach, Gretchen L., Veenstra, Timothy D., Falk, Roni T., Nichols, Kathryn, Guttmann, Allison, Xu, Xia, Greene, Mark H., Gail, Mitchell H.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.02.2014; Springer; Springer Nature B.V
• Subjects: Adult; BRCA1 Protein - genetics; BRCA2 Protein - genetics; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Cancer research; Carcinogenesis - genetics; Carcinogenesis - metabolism; Clinical Trial; Estradiol - blood; Estradiol - metabolism; Estrogen; Estrogens; Estrone - blood; Estrone - metabolism; Female; Fluorides; Genetic aspects; Heterozygote; Hormones; Humans; Liquid chromatography; Mass spectrometry; Medicine; Medicine & Public Health; Metabolites; Middle Aged; Mutation; Nipple Aspirate Fluid; Oncology; Postmenopausal women; Postmenopause; Premenopause; Tandem Mass Spectrometry; Tissues; Parent estrogens; Postmenopausal; BRCA1/2; Nipple aspirate fluid; Ductal lavage supernatant; LC/MS/MS; Estrogens; Estrogen metabolites
• ISSN: 0167-6806; 1573-7217; 1573-7217
• DOI: 10.1007/s10549-013-2821-6

Accurately quantifying parent estrogens (PE) estrone (E 1 ) and estradiol (E 2 ) and their metabolites (EM) within breast tissue and serum may permit detailed investigations of their contributions to breast carcinogenesis among BRCA1/2 mutation carriers. We conducted a study of PE/EM in serum, nipple aspirate fluid (NAF), and ductal lavage supernatant (DLS) among postmenopausal BRCA1/2 mutation carriers. PE/EM (conjugated and unconjugated) were measured in paired serum/NAF ( n  = 22 women) and paired serum/DLS samples ( n  = 24 women) using quantitative liquid chromatography–tandem mass spectrometry (LC/MS/MS). The relationships between serum and tissue-specific PE/EM were measured using Pearson’s correlation coefficients. Conjugated forms of PE/EM constituted the majority of estrogen in serum (88 %), NAF (59 %) and DLS (69 %). PE/EM in NAF and serum were highly correlated [E 1 ( r  = 0.97, p  < 0.0001), E 2 ( r  = 0.90, p  < 0.0001) and estriol (E 3 ) ( r  = 0.74, p  < 0.0001)] as they were in DLS and serum [E 1 ( r  = 0.92, p  < 0.0001; E 2 ( r  = 0.70, p  = 0.0001; E 3 ( r  = 0.67, p  = 0.0004)]. Analyses of paired total estrogen values for NAF and serum, and DLS and serum yielded ratios of 0.22 (95 % CI 0.19–0.25) and 0.28 (95 % CI 0.24–0.32), respectively. This report is the first to employ LC/MS/MS to quantify PE/EM in novel breast tissue-derived biospecimens (i.e., NAF and DLS). We demonstrate that circulating PE and EM are strongly and positively correlated with tissue-specific PE and EM measured in NAF and DLS among postmenopausal BRCA1/2 mutation carriers. If confirmed, future etiologic studies could utilize the more readily obtainable serum hormone levels as a reliable surrogate measure of exposure at the tissue level.