Comparative Biomarker Analysis in 523 Matched Male and Female Breast Cancers.

Abstract

Incidence rates of male breast cancer (MBC) are rising. MBC etiology is poorly understood with most of our current knowledge regarding its biology, natural history and treatment extrapolated from our knowledge of female breast cancer (FBC). Retrospective studies on MBC have suffered from small numbers of cases available from any one centre thus a significant problem in studying this disease is accruing sufficiently large numbers to allow comparative analysis of possible prognostic markers. Using a co-ordinated multi-centre approach, the aim of this study was to conduct the first large scale study to address the relevance of the expression of recognised biomarkers in FBC in the same disease in males. Five hundred and twenty three cases were obtained retrospectively and assimilated into TMAs, including 260 MBCs and 263 cases of stage-matched FBCs. MBC comprised 21 grade 1, 121 grade 2, 68 grade 3, 50 unknown, mean age 67 (range 39-90) with 167 ductal, 4 lobular, 10 papillary, 10, mucinous, 4 DCIS, 1 mixed and 64 unknown. FBC comprised 29 grade 1, 140 grade 2, 94 grade, mean age 58 (range 27-92) with 220 ductal, 23 lobular, 14 mixed and 6 unknown. Four µm TMA sections were analysed using the following biomarkers: hormone receptors (ERα, ERβ1, ERβ2, ERβ5, total PR, PRA, PRB, AR), apoptosis markers (p53, bcl2), basal (CK5/6, CK14) and luminal epithelial markers (CK18, CK19), E-cadherin and HER2. Biomarkers were scored according to published criteria; for ERβ isoforms both nuclear and cytoplasmic immunoreactivity was determined Statistical analysis was conducted using SPSS. Luminal A (ERα+, and/or PR+, HER2-) was seen in 93% of MBC vs. 84% of FBC, Luminal B (ERα+, and/or PR+, HER2+) or HER2 subgroup (ERα-, PR-, HER2+) was not seen in MBC but found in 6% and 2% of FBC, respectively. Basal-like tumours (ERα-, PR-, HER2-, CK5/6+) were infrequent (MBC 2%, FBC 1%) and in MBC these tumours also expressed ERβ isoforms. No differences were observed in grade, stage or LN status between genders. Univariate analysis showed ERα, ERβ1, ERβ5, PRA, AR, p53 were significantly associated with FBC while cytoplasmic ERβ2, bcl2 and e-cadherin were associated with MBC (all P<0.001). Although membranous HER2 was not seen in MBC, many cases displayed nuclear staining. Biomarker profile with respect to clinical outcome is on-going. This work has shown the luminal A phenotype is common in MBC and that gender-specific biomarkers are expressed. As MBC is becoming more common, this information may be useful in identifying biomarkers which might affect outcome. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2109.