Journal
BREAST CANCER RESEARCH AND TREATMENT
Volume 134, Issue 1, Pages 411-418Publisher
SPRINGER
DOI: 10.1007/s10549-012-2062-0
Keywords
Male breast cancer; BRCA1; BRCA2; Clinical-pathologic features; Molecular subtypes
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Funding
- Associazione Italiana per la Ricerca sul Cancro [AIRC IG 8713]
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Recently, the number of studies on male breast cancer (MBC) has been increasing. However, as MBC is a rare disease there are difficulties to undertake studies to identify specific MBC subgroups. At present, it is still largely unknown whether BRCA-related breast cancer (BC) in men may display specific characteristics as it is for BRCA-related BC in women. To investigate the clinical-pathologic features of MBC in association with BRCA mutations we established a collaborative Italian Multicenter Study on MBC with the aim to recruit a large series of MBCs. A total of 382 MBCs, including 50 BRCA carriers, were collected from ten Italian Investigation Centres covering the whole country. In MBC patients, BRCA2 mutations were associated with family history of breast/ovarian cancer (p < 0.0001), personal history of other cancers (p = 0.044) and contralateral BC (p = 0.001). BRCA2-associated MBCs presented with high tumor grade (p = 0.001), PR- (p = 0.026) and HER2+ (p = 0.001) status. In a multivariate logistic model BRCA2 mutations showed positive association with personal history of other cancers (OR 11.42, 95 % CI 1.79-73.08) and high tumor grade (OR 4.93, 95 % CI 1.02-23.88) and inverse association with PR+ status (OR 0.19, 95 % CI 0.04-0.92). Based on immunohistochemical (IHC) profile, four molecular subtypes of MBC were identified. Luminal A was the most common subtype (67.7 %), luminal B was observed in 26.5 % of the cases and HER2 positive and triple negative were represented by 2.1 % and 3.7 % of tumors, respectively. Intriguingly, we found that both luminal B and HER2 positive subtypes were associated with high tumor grade (p = 0.003 and 0.006, respectively) and with BRCA2 mutations (p = 0.016 and 0.001, respectively). In conclusion, our findings indicate that BRCA2-related MBCs represent a subgroup of tumors with a peculiar phenotype characterized by aggressive behavior. The identification of a BRCA2-associated phenotype might define a subset of MBC patients eligible for personalized clinical management.
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