Endocrine Biomarkers in Ductal Lavage Samples from Women at High Risk for Breast Cancer

Bhandare, Deepa; Nayar, Ritu; Bryk, Michelle; Hou, Nanjiang; Cohn, Rachel; Golewale, Nazar; Parker, Noah P.; Chatterton, Robert T.; Rademaker, Alfred; Khan, Seema A.

doi:10.1158/1055-9965.epi-05-0302

Cited by 22 publications

(27 citation statements)

References 24 publications

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“…So far, we have seen reassuring stability of ER expression over two time points 6 months apart, when the second sample is obtained in the same phase of the menstrual cycle as the first (Bhandare et al 2003). Our on-going study will also provide information as to whether or not high ERa expression in benign or atypical epithelium identifies women more likely to benefit from endocrine prevention strategies.…”

Section: Era Data From Studies Using Minimal Sampling Techniquesmentioning

confidence: 69%

The local hormonal environment and related biomarkers in the normal breast

Khan¹,

Bhandare²,

Chatterton³

2005

Endocr Relat Cancer

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Recent developments in breast epithelial sampling techniques (nipple fluid aspiration, ductal lavage, and random fine needle aspiration) provide new opportunities for the acquisition of hormonal and cellular biomarker data in asymptomatic women, and thereby the possibility of developing a unified vision of how the hormonal environment of the breast may interact with the cellular expression of proteins, and with other evolving candidate markers of breast cancer risk. The purpose of this review is to integrate available information regarding cellular and breast fluid biomarkers of hormone action on the breast, to identify candidate biomarkers for studies of breast cancer risk and prevention. These include the estrogen receptors a and b, markers of proliferative and apoptotic response, and protein markers of estrogen action in breast cells and nipple fluid. Studies of breast hormone levels in nipple aspiration fluid (NAF) show that estrone sulphate is present in large quantities in the normal breast, while the differences in serum ovarian steroids that are seen in preand postmenopausal women are blunted in NAF. The variability of several estradiol precursors in NAF over time is relatively small, a useful attribute of potential biomarkers of breast cancer risk, particularly if they are reversible with intervention in Phase 2 prevention trials. These studies are already providing new insights into the hormonal etiology of breast cancer, and should lead to the identification of robust, reversible biomarkers for use in breast cancer prevention studies.

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Section: Era Data From Studies Using Minimal Sampling Techniquesmentioning

confidence: 69%

The local hormonal environment and related biomarkers in the normal breast

Khan¹,

Bhandare²,

Chatterton³

2005

Endocr Relat Cancer

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“…Data on the relationship between hormones in NAF, ductal lavage supernatant (DLS), and hormone concentrations in serum are inconsistent in both pre- and postmenopausal women [23, 30–32]. NAF estrogen concentrations have been reported as being higher than serum estrogen levels, and some studies have suggested a greater postmenopausal decline in serum estrogen levels than in NAF [31, 33, 34]. Most recently, correlations between serum and NAF estrogen levels in healthy postmenopausal women presenting for routine breast cancer surveillance ( n = 18) were reported as low (E 1 , r = −0.23 [ P = 0.25] E 2 , r = 0.14 [ P = 0.47]) [31, 34].…”

Section: Introductionmentioning

confidence: 99%

“…NAF estrogen concentrations have been reported as being higher than serum estrogen levels, and some studies have suggested a greater postmenopausal decline in serum estrogen levels than in NAF [31, 33, 34]. Most recently, correlations between serum and NAF estrogen levels in healthy postmenopausal women presenting for routine breast cancer surveillance ( n = 18) were reported as low (E 1 , r = −0.23 [ P = 0.25] E 2 , r = 0.14 [ P = 0.47]) [31, 34]. The correlation between circulating and intra-breast levels (e.g., in NAF or DLS) has not been evaluated in BRCA1/2 mutation-positive women.…”

Section: Introductionmentioning

confidence: 99%

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

Loud

Gierach

Veenstra

et al. 2014

Breast Cancer Res Treat

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Accurately quantifying parent estrogens (PE) estrone (E1) and estradiol (E2) 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 [E1 (r = 0.97, p < 0.0001), E2 (r = 0.90, p < 0.0001) and estriol (E3) (r = 0.74, p < 0.0001)] as they were in DLS and serum [E1 (r = 0.92, p < 0.0001; E2 (r = 0.70, p = 0.0001; E3 (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 post-menopausal 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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“…Ductal lavage has the advantage that epithelial cells that are shed from the ducts may be obtained for assessment of atypical forms from the breasts of healthy high-risk women [17]. We have previously reported initial results from a Phase 2 prevention study designed to assess the utility of ductal lavage for the measurement of cellular markers of breast cancer risk and tamoxifen response in a population at increased risk of breast cancer [18]. Tamoxifen-eligible women either accepted or declined tamoxifen therapy after appropriate counseling, and all subjects were asked to return for a six-month follow-up procedure which included ductal lavage.…”

Section: Introductionmentioning

confidence: 99%

Breast Ductal Lavage for Assessment of Breast Cancer Biomarkers

et al. 2010

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Purpose Lavage of the ductal systems of the breast provides fluid (DLF) containing hormones and products of hormone actions that may represent more accurately the composition of the breast than samples collected from blood or urine. The present study was undertaken to assess the presence of potential cancer biomarkers, their variation among individuals at high risk for breast cancer, and differences associated with menopause and tamoxifen treatment. Methods Seventy seven tamoxifen-eligible subjects with a 5-year breast cancer risk estimate (Gail > 1.6%)(N = 53) or recently diagnosed breast cancer (N = 24) were offered tamoxifen therapy; those not accepting tamoxifen were under observation only. After six months, all subjects underwent ductal lavage (DL) in an unaffected breast. Estradiol (E2), estrone sulfate, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulfate, progesterone, cathepsin D and epidermal growth factor (EGF) were measured in DLF by immunoassays. Data were expressed as the mass of analyte per mg of protein in DLF and normalized by natural log transformation. Results With the exception of DHEA, none of the analytes measured were significantly lower in postmenopausal women than in premenopausal women. The mean loge concentration difference in estradiol was 10.9%. Tamoxifen treatment for 6 months did not result in a significantly greater concentration of E2 or in any of the other analytes in DLF of pre- or postmenopausal women. The between-duct variance of the concentration of free steroids within the same breast averaged 51% less than that between subjects, and was similar to that of non-diffusible proteins. Conclusions The maintenance of estradiol concentrations in the breast after menopause demonstrates the importance of local biosynthesis. The fact that DLF E2 does not reflect the high serum concentrations of E2 during tamoxifen treatment indicates that breast concentrations of estradiol may be under feedback control. Unlike studies of low risk populations, progesterone concentrations were not significantly less in postmenopausal than in premenopausal women. The similarity in variance of free steroids and protein analytes between ducts of a breast indicates little transfer of steroids between lobules.

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Endocrine Biomarkers in Ductal Lavage Samples from Women at High Risk for Breast Cancer

Cited by 22 publications

References 24 publications

The local hormonal environment and related biomarkers in the normal breast

The local hormonal environment and related biomarkers in the normal breast

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

Breast Ductal Lavage for Assessment of Breast Cancer Biomarkers

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