Androgens and androgen receptors: A clinically neglected sector in breast cancer biology

Moe, Roger E.; Anderson, Benjamin O.

doi:10.1002/jso.20722

Cited by 31 publications

(27 citation statements)

References 7 publications

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“…AR typically is present in a greater proportion of breast tumors (80-90%) than ERa (50-80%; reviewed in refs. 5,9) and previous studies have indicated the potential for AR to predict disease progression (10,11). In addition, we have reported that the level of the AR predicts both the likelihood and the duration of response to therapy with the synthetic progestin, medroxyprogesterone acetate (12), and that disease progression after medroxyprogesterone acetate therapy is associated with inactivating mutations in the AR gene (13).…”

Section: Introductionmentioning

confidence: 68%

Androgen Receptor Inhibits Estrogen Receptor-α Activity and Is Prognostic in Breast Cancer

et al. 2009

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There is emerging evidence that the balance between estrogen receptor-A (ERA) and androgen receptor (AR) signaling is a critical determinant of growth in the normal and malignant breast. In this study, we assessed AR status in a cohort of 215 invasive ductal breast carcinomas. AR and ERA were coexpressed in the majority (80-90%) of breast tumor cells. KaplanMeier product limit analysis and multivariate Cox regression showed that AR is an independent prognostic factor in ERApositive disease, with a low level of AR (less than median of 75% positive cells) conferring a 4.6-fold increased risk of cancer-related death (P = 0.002). Consistent with a role for AR in breast cancer outcome, AR potently inhibited ERA transactivation activity and 17B-estradiol-stimulated growth of breast cancer cells. Transfection of MDA-MB-231 breast cancer cells with either functionally impaired AR variants or the DNA-binding domain of the AR indicated that the latter is both necessary and sufficient for inhibition of ERA signaling. Consistent with molecular modeling, electrophoretic mobility shift assays showed binding of the AR to an estrogenresponsive element (ERE). Evidence for a functional interaction of the AR with an ERE in vivo was provided by chromatin immunoprecipitation data, revealing recruitment of the AR to the progesterone receptor promoter in T-47D breast cancer cells. We conclude that, by binding to a subset of EREs, the AR can prevent activation of target genes that mediate the stimulatory effects of 17B-estradiol on breast cancer cells. [Cancer Res 2009;69(15):6131-40]

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Section: Introductionmentioning

confidence: 68%

Androgen Receptor Inhibits Estrogen Receptor-α Activity and Is Prognostic in Breast Cancer

et al. 2009

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“…Consequently, our results clearly separated breast tumors with apocrine cytomorphology into two different groups: the pure apocrine carcinomas with consistent lack of ER and overexpression of AR, and morphologically apocrine-like carcinomas that did not exhibit the protein expression profile associated with the true apocrine phenotype. 4,5,13,32 Similarly, Celis et al 8 using another set of morphological and immunohistochemical criteria for classification of apocrine carcinoma defined and confirmed the existence of a distinct apocrine carcinoma group with a consistent steroid receptor profile (ERÀ, AR þ ). Together, these results strongly support the recent advances in molecular classification of breast carcinoma that have revealed the existence of a specific 'molecular apocrine' gene expression profile among ER-negative breast carcinomas characterized primarily by increased AR signaling, along with a common Her-2/neu gene amplification.…”

Section: Discussionmentioning

confidence: 88%

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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“…In breast cancer (BC), AR is expressed in 50-88% of cases [8][9][10][11][12][13][14] with an average of 61% in all BCs and 75% in ER-positive tumours [15]. Previous studies have shown that AR expression has the potential to predict disease progression [15,16], as well as the likelihood and duration of response to therapy when used with medroxyprogesterone acetate [17].…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of androgen receptor expression in invasive breast cancer: transcriptomic and protein expression analysis

Aleskandarany

Abduljabbar

Ashankyty

et al. 2016

Breast Cancer Res Treat

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Androgens and androgen receptors: A clinically neglected sector in breast cancer biology

Cited by 31 publications

References 7 publications

Androgen Receptor Inhibits Estrogen Receptor-α Activity and Is Prognostic in Breast Cancer

Androgen Receptor Inhibits Estrogen Receptor-α Activity and Is Prognostic in Breast Cancer

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

Prognostic significance of androgen receptor expression in invasive breast cancer: transcriptomic and protein expression analysis

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