期刊
BREAST CANCER RESEARCH AND TREATMENT
卷 143, 期 3, 页码 517-529出版社
SPRINGER
DOI: 10.1007/s10549-013-2821-6
关键词
BRCA1/2; Estrogens; Parent estrogens; Estrogen metabolites; Nipple aspirate fluid; Ductal lavage supernatant; LC/MS/MS; Postmenopausal
类别
资金
- Intramural Research Program of the National Cancer Institute
- Westat, Inc. [NO2-CP-11019-50, NO2-CP-65504-50]
- Molecular Epidemiology Award from Division of Cancer Epidemiology and Genetics, National Cancer Institute
- National Cancer Institute, National Institutes of Health [HHSN261200800001E]
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.
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