Clinical and pathologic characteristics of BRCA-positive and BRCA-negative male breast cancer patients: results from a collaborative multicenter study in Italy

Abstract

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 BRCArelated 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 -012-2062-0 association with personal history of other cancers (OR 11.42,) and high tumor grade (OR 4.93,) and inverse association with PR? status (OR 0.19,). 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.123 Breast Cancer Res Treat (2012) 134:411-418 DOI 10.1007/s10549

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

“…The need for more refined therapeutic treatments for male breast cancer (MBC) is evidenced by a steady stream of publications highlighting gender-specific differences using IHC (1-5), genetics (6)(7)(8)(9)(10)(11), and more recently, epigenetics (12)(13)(14)(15). Of note, although MBC is similar histologically to female breast cancer (FBC), with the same panel of biomarkers used to guide treatment and prognosis, more rigorous interrogation of the underlying genetics shows heterogeneity in MBC as recognized in FBC where molecular profiling has identified different subgroups that correlate with varying clinical outcomes.…”

Association of low-penetrance alleles with male breast cancer risk and clinicopathological characteristics: results from a multicenter study in Italy

“…Intriguingly, we have recently shown that HER2? subtype was associated with BRCA2 mutations in MBC [10]. Although based on small number of cases, these results may suggest that the observed associations between susceptibility loci and ER/ PR status may reflect underlying associations with particular molecular profiles.…”

“…All subjects were recruited from ten Italian Investigation Centers distributed across the country in the frame of the ongoing Italian Multicenter Study on MBC [10]. Information collected for each MBC case included: age at diagnosis, family and personal history of cancer, recurrence of the disease, BRCA1/2 mutation status, tumor histological type, grade (G), node (N) status, ER, PR, Ki-67, and HER2 expression.…”

“…status [3]. We recently showed that BRCA2-related MBCs represent a subgroup of tumors with a peculiar phenotype characterized by high tumor grade, the absence of PR expression and HER2 positive status [10], thus providing evidence that high-penetrance genetic factors can also influence tumor type in MBC. This raises the possibility that other susceptibility loci may also be associated with specific subtypes of MBC.…”

“…Rare variants in moderate-penetrance BC susceptibility genes, including CHEK2, BRIP1, PALB2, and RAD51C, may also play a role in MBC, although at lower extent [7]. We recently reported that only a small proportion (about 14 %) of MBCs is accounted by high-and moderate penetrance BC susceptibility genes in Italy [8][9][10]. Thus, much of the genetic contribution to MBC risk remains to be elucidated.…”