Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family

Sanga, Sandeep; Broom, Bradley M.; Cristini, Vittorio; Edgerton, Mary E.

doi:10.1186/1755-8794-2-59

Cited by 44 publications

(41 citation statements)

References 60 publications

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“…Androgens also enhance activation of ERK, a downstream effector of HER2, and HER2-AR crosstalk is required for proliferation and viability of molecular apocrine breast cancer cell lines (Naderi & Hughes-Davies 2008, a concept that is supported by bioinformatic analysis of gene expression profiles in molecular apocrine breast cancer tissues (Sanga et al 2009). This reveals that AR and FOXA1 utilise a complex regulatory network to enhance the tumourigenic potential of breast cancer cells, at least in a molecular apocrine context.…”

Section: Ar Foxa1 and Her2mentioning

confidence: 99%

Complexities of androgen receptor signalling in breast cancer

McNamara¹,

Moore²,

Hickey³

et al. 2014

Endocrine-Related Cancer

123

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While the clinical benefit of androgen-based therapeutics in breast cancer has been known since the 1940s, we have only recently begun to fully understand the mechanisms of androgen action in breast cancer. Androgen signalling pathways can have either beneficial or deleterious effects in breast cancer depending on the breast cancer subtype and intracellular context. This review discusses our current knowledge of androgen signalling in breast cancer, including the relationship between serum androgens and breast cancer risk, the prognostic significance of androgen receptor (AR) expression in different breast cancer subtypes and the downstream molecular pathways mediating androgen action in breast cancer cells. Intracrine androgen metabolism has also been discussed and proposed as a potential mechanism that may explain some of the reported differences regarding dichotomous androgen actions in breast cancers. A better understanding of AR signalling in this disease is critical given the current resurgence in interest in utilising contemporary AR-directed therapies for breast cancer and the need for biomarkers that will accurately predict clinical response.

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Section: Ar Foxa1 and Her2mentioning

confidence: 99%

Complexities of androgen receptor signalling in breast cancer

McNamara¹,

Moore²,

Hickey³

et al. 2014

Endocrine-Related Cancer

123

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“…[13][14][15][16] This molecular apocrine group was characterized by increased AR signaling along with increased human epidermal growth factor receptor 2 (HER-2)/neu gene signaling. 13,16 A study using an apocrine cell line model also demonstrated the existence of a functionally significant cross-talk between AR and HER-2/neu pathways through ERK1/2 in ER-negative breast carcinomas. 17 This cross-talk affects cell proliferation and apoptosis and could have a significant therapeutic impact.…”

mentioning

confidence: 99%

EGFR and HER-2/neu expression in invasive apocrine carcinoma of the breast

et al. 2010

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This study was undertaken to investigate epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2)/neu expression in a cohort of apocrine carcinomas of the breast with emphasis on the classification of the breast tumors with apocrine morphology. In total, 55 breast carcinomas morphologically diagnosed as apocrine were evaluated for the steroid receptor expression profile characteristic of normal apocrine epithelium (androgen receptor positive/estrogen receptor (ER) negative/progesterone receptor (PR) negative), and for the expression of EGFR and Her-2/neu proteins, and the copy number ratios of the genes EGFR/CEP7 and HER-2/CEP17. On the basis of the results of steroid receptors expression, 38 (69%) cases were classified as pure apocrine carcinoma (androgen receptor positive/ER negative/PR negative), whereas 17 (31%) were re-classified as apocrine-like carcinomas because they did not have the characteristic steroid receptor expression profile. Her-2/neu overexpression was observed in 54% of the cases (57% pure apocrine carcinomas vs 47% apocrine-like carcinomas). HER-2/neu gene amplification was demonstrated in 52% of all cases (54% pure apocrine carcinomas vs 46% apocrine-like carcinomas). EGFR protein (scores 1 to 3 þ ) was detected in 62% of all cases and was expressed in a higher proportion of pure apocrine carcinomas than in the apocrine-like carcinomas group (76 vs 29%, P ¼ 0.006). In the pure apocrine carcinoma group, Her-2/ neu and EGFR protein expression were inversely correlated (P ¼ 0.006, r ¼ À0.499). EGFR gene amplification was observed in two pure apocrine carcinomas and one apocrine-like carcinoma. Polysomy 7 was commonly present in pure apocrine carcinomas (61 vs 27% of apocrine-like carcinomas; P ¼ 0.083) and showed a weak positive correlation with EGFR protein expression (P ¼ 0.025, r ¼ 0.326). Our study showed that apocrine breast carcinomas are molecularly diverse group of carcinomas. Strictly defined pure apocrine carcinomas are either HER-2-overexpressing breast carcinomas or triple-negative breast carcinomas, whereas apocrine-like carcinomas predominantly belong to the luminal phenotype. Pure apocrine carcinomas show consistent overexpression of either EGFR or HER-2/neu, which could have significant therapeutic implications.

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“…33 A ''normal breast-like'' subtype has been identified, but its existence has been questioned on the grounds that many of the normal breast-like tumors have been paucicellular and therefore have consisted mainly of nontumor tissue, 33 which of course, upon expression profiling, resembled normal breast. Rare intrinsic subtypes include claudin-low, with low expression of cell adhesion genes, 34 and molecular apocrine-like, 35 which often expresses androgen receptors. 36 …”

Section: Basis Of Testmentioning

confidence: 99%

Molecular Testing in Breast Cancer: A Guide to Current Practices

Hagemann

2016

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Molecular diagnostics play a role in the management of many cancers, including breast cancer.Objective.-To provide an update on molecular testing in current clinical practice, targeted at practicing pathologists who are not breast cancer specialists.Data Sources.-This study is a narrative literature review.Conclusions.-In addition to routine hormone (estrogen and progesterone) receptor testing, new and recurrent tumors are tested for HER2 amplification by in situ hybridization or overexpression by immunohistochemistry. Intrinsic subtyping of tumors represents a fundamental advance in our understanding of breast cancer biology, but currently it has an indirect role in patient management. Clinical next-generation sequencing (tumor profiling) is increasingly used to identify potentially actionable mutations in tumor tissue. Multianalyte assays with algorithmic analysis, including MammaPrint, Oncotype DX, and Prosigna, play a larger role in breast cancer than in many other malignancies. Given that a proportion of breast cancers are familial, testing of nontumor tissue for cancer predisposition mutations also plays a role in breast cancer care.

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Gene expression meta-analysis supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB family

Cited by 44 publications

References 60 publications

Complexities of androgen receptor signalling in breast cancer

Complexities of androgen receptor signalling in breast cancer

EGFR and HER-2/neu expression in invasive apocrine carcinoma of the breast

Molecular Testing in Breast Cancer: A Guide to Current Practices

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