BRCA1/BRCA2 mutation status and clinical-pathologic features of 108 male breast cancer cases from Tuscany: a population-based study in central Italy

Abstract

To investigate the genetic and phenotypic characteristics of MBC in a large and well-characterized population-based series of 108 MBCs from Tuscany (Central Italy) and to evaluate associations between BRCA1/BRCA2 mutation status and clinical-pathological features including breast/ovarian cancer first-degree family history, tumor histology and grade, proliferative activity, estrogen/progesterone receptors (ER/PR) and epidermal growth factor receptor 2 (HER2) expression. Results BRCA1/BRCA2 mutations were identified in ten MBCs, in particular, two cases (1.9%) carried BRCA1 and eight cases (7.4%) carried BRCA2 mutations. The same BRCA1 mutation (3347delAG) was detected in two unrelated MBC cases. Three novel BRCA2 pathogenic mutations were found. Statistically significant associations emerged between BRCA2-related tumors and absence of PR expression (P = 0.008), HER2 over-expression (P = 0.002) and high tumor grade (P = 0.005). Conclusions Here, we (i) reported that in our population about 9% of MBC cases are accounted for by BRCA1/BRCA2 mutations; (ii) enlarged the BRCA2 mutational spectrum and (iii) characterized a specific phenotype associated with BRCA2-related MBCs suggestive of aggressive behavior. Overall, our results may have important implications on clinical management for this rare disease.

Male breast cancer: Risk factors, diagnosis, and management (Review)

“…The association between BRCA1 mutations and MBC is not as strong as that seen for BRCA2 mutations. The lifetime risk for breast cancer in a male BRCA1 mutation carrier is just over 1%, and it is estimated that a BRCA1 mutation is present in up to 4% of MBC cases (13,25,26).…”

The BRCAPRO 5.0 model is a useful tool in genetic counseling and clinical management of male breast cancer cases

“…In this context, it is noteworthy that we have recently described the phenotypic characteristics of BRCA1/2-related MBCs and shown that a specific phenotype that included HER2 over-expression was associated with BRCA2-related MBCs. 16 In conclusion, the BRCAPRO 5.0 model, together with an experienced clinical evaluation, is a useful tool in selecting cases of male breast cancer for mutation analysis in the presence of MBC cases with a negative FH. In this context, the BRCAPRO 5.0 model performs better in taking account of personal history of cancer and selected tumour characteristics.…”

“…Overall, 38% (39/102) of the patients reported a first-and/or second-degree breast-ovarian cancer FH, eight cases (8/102, 7.8%) carried a BRCA2 mutation and two cases (2/102, 2.0%) carried the same founder BRCA1 mutation. 16,18 Six of the 10 mutation carriers had a positive FH. Thus, mutation carriers account for 15.4% (6/39) of our male probands with a positive FH and for 6.4% (4/63) of those without a positive FH.…”

“…The recruitment of the cases and the BRCA1/2 mutational analysis were carried out as recently described. 16,17 Briefly, the recruitment of all incident MBC cases was based on all currently available local sources (including pathology departments and the hospital discharge database). For each case index the entire coding sequence and each intron-exon boundary were screened for germline mutations by combining the protein truncation test (PTT), single-strand conformation polymorphism (SSCP), multiplex ligation-dependent probe amplification (MLPA) and direct sequencing.…”

“…However, the majority of MBC patients do not have a positive family history (FH) of BC and our previous studies, performed on a large population-based series of MBCs, demonstrate that the majority of MBC cases are not accounted for by BRCA1/2 alterations. 16 …”