Characterisation of male breast cancer: a descriptive biomarker study from a large patient series

Abstract

Male breast cancer (MBC) is rare. We assembled 446 MBCs on tissue microarrays and assessed clinicopathological information, together with data from 15 published studies, totalling 1984 cases. By immunohistochemistry we investigated 14 biomarkers (ERα, ERβ1, ERβ2, ERβ5, PR, AR, Bcl-2, HER2, p53, E-cadherin, Ki67, survivin, prolactin, FOXA1) for survival impact. The main histological subtype in our cohort and combined analyses was ductal (81%, 83%), grade 2; (40%, 44%), respectively. Cases were predominantly ERα (84%, 82%) and PR positive (74%, 71%), respectively, with HER2 expression being infrequent (2%, 10%), respectively. In our cohort, advanced age (>67) was the strongest predictor of overall (OS) and disease free survival (DFS) (p = 0.00001; p = 0.01, respectively). Node positivity negatively impacted DFS (p = 0.04). FOXA1 p = 0.005) and AR p = 0.009) were both positively prognostic for DFS, remaining upon multivariate analysis. Network analysis showed ERα, AR and FOXA1 significantly correlated. In summary, the principle phenotype of MBC was luminal A, ductal, grade 2. In ERα+ MBC, only AR had prognostic significance, suggesting AR blockade could be employed therapeutically.

Figure 1. Kaplan-Meier survival analysis.

Kaplan-Meier survival analysis showing the impact of FOXA1 expression on OS (a) and DFS (b), the effect of AR expression on DFS (c) and the impact of AR and FOXA1 co-expression on OS (d) and DFS (e). The number of at risk patients and events over time are displayed under each graph.

Figure 2. Correlative biomarker relationships.

Dendrogram showing biomarker correlations using agglomerative hierarchical clustering with complete linkage (a) with an example protein network (b) showing significant correlation relationships indicated by the thickness of line connections. Nodes range from blue to orange, indicating low to high degree of significance, respectively. P values are displayed on the image.