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Androgen receptor expression in normal breast tissue and subsequent breast cancer risk.

ABSTRACT: Sex steroid hormone signaling is critical in the development of breast cancers, although the role of the androgen receptor remains unclear. This study evaluated androgen receptor (AR) expression in normal breast tissue as a potential marker of breast cancer risk. We conducted a nested case-control study of women with benign breast disease (BBD) within the Nurses' Health Studies. Epithelial AR expression was assessed by immunohistochemistry in normal tissue from the BBD biopsy and the percent of positive nuclei was estimated in ordinal categories of 10% for 78 breast cancer cases and 276 controls. Logistic regression models adjusting for the matching factors and BBD lesion type were used to calculate odds ratios (ORs) for the association between AR expression (tertiles: ?10%, 11-30%, and >30%) and breast cancer risk. AR expression in normal breast tissue was not associated with subsequent breast cancer risk (ORT3vsT1?=?0.9, 95% CI?=?0.4-1.8, p trend?=?0.68). In comparison with low AR/low ER women, ORs of 0.4 (95% CI?=?0.1-1.2) for high AR/high ER women, 1.8 (95% CI?=?0.4-7.8) for low AR/high ER women, and 0.7 (95% CI?=?0.3-1.6) for high AR/low ER women were observed (p interaction?=?0.21). Ki67 did not modify the association between AR expression and breast cancer risk (p interaction?=?0.75). There was little evidence for an overall association between AR expression in normal breast tissue and breast cancer risk. These findings did not show that the AR association varied by Ki67 expression in normal breast tissue, though there was suggestive heterogeneity by ER expression.

SUBMITTER: Kensler KH

PROVIDER: S-EPMC6155011 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Androgen receptor expression in normal breast tissue and subsequent breast cancer risk.

Kensler Kevin H KH Beca Francisco F Baker Gabrielle M GM Heng Yujing J YJ Beck Andrew H AH Schnitt Stuart J SJ Hazra Aditi A Rosner Bernard A BA Eliassen A Heather AH Hankinson Susan E SE Brown Myles M Tamimi Rulla M RM

NPJ breast cancer 20180921

Sex steroid hormone signaling is critical in the development of breast cancers, although the role of the androgen receptor remains unclear. This study evaluated androgen receptor (AR) expression in normal breast tissue as a potential marker of breast cancer risk. We conducted a nested case-control study of women with benign breast disease (BBD) within the Nurses' Health Studies. Epithelial AR expression was assessed by immunohistochemistry in normal tissue from the BBD biopsy and the percent of ...[more]

PMID: 30276234

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Project description:PurposeAndrogen receptor (AR) is frequently detected in breast cancers, and AR-targeted therapies are showing activity in AR-positive (AR+) breast cancer. However, the role of AR in breast cancers is still not fully elucidated and the biology of AR in breast cancer remains incompletely understood. Circulating tumor cells (CTCs) can serve as prognostic and diagnostic tools, prompting us to measure AR protein expression and conduct genomic analyses on CTCs in patients with metastatic breast cancer.MethodsBlood samples from patients with metastatic breast cancer were deposited on glass slides, subjected to nuclear staining with DAPI, and reacted with fluorescent-labeled antibodies to detect CD45, cytokeratin (CK), and biomarkers of interest (AR, estrogen receptor [ER], and HER2) on all nucleated cells. The stained slides were scanned and enumerated by non-enrichment-based non-biased approach independent of cell surface epithelial cell adhesion molecule (EpCAM) using the Epic Sciences CTC platform. Data were analyzed using established digital pathology algorithms.ResultsOf 68 patients, 51 (75%) had at least 1 CTC, and 49 of these 51 (96%) had hormone-receptor-positive (HR+)/HER2-negative primary tumors. AR was expressed in CK+ CTCs in 10 patients. Of these 10 patients, 3 also had ER expression in CK+ CTCs. Single cell genomic analysis of 78 CTCs from 1 of these 3 patients identified three distinct copy number patterns. AR+ cells had a lower frequency of chromosomal changes than ER+ and HER2+ cells.ConclusionsCTC enumeration and analysis using no enrichment or selection provides a non-biased approach to detect AR expression and chromosomal aberrations in CTCs in patients with metastatic breast cancer. The heterogeneity of intrapatient AR expression in CTCs leads to the new hypothesis that patients with AR+ CTCs have heterogeneous disease with multiple drivers. Further studies are warranted to investigate the clinical applicability of AR+ CTCs and their heterogeneity.

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Androgen receptor expression in normal breast tissue and subsequent breast cancer risk.

Publications

Androgen receptor expression in normal breast tissue and subsequent breast cancer risk.

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