title: BRCA1/BRCA2 mutation status and clinical-pathologic features of 108 male breast cancer cases from Tuscany: a population-based study in central Italy.
abstract: BACKGROUND
  Male breast cancer (MBC) is a rare and scarcely investigated disease. The strongest genetic risk factor for MBC is represented by inherited BRCA2 mutations, whereas the association between MBC and BRCA1 mutations is less clear. MBC appears to be biologically similar to breast cancer in females, however the phenotypic characteristics of BRCA1/2-related MBCs are not yet well elucidated.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Experimental Medicine, University of Rome La Sapienza, 00161 Rome, Italy. laura.ottini@uniroma1.it
authors.forename: Laura
authors.initials: L
authors.lastname: Ottini
authors.forename: Piera
authors.initials: P
authors.lastname: Rizzolo
authors.forename: Ines
authors.initials: I
authors.lastname: Zanna
authors.forename: Mario
authors.initials: M
authors.lastname: Falchetti
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.forename: Ketty
authors.initials: K
authors.lastname: Ceccarelli
authors.forename: Vania
authors.initials: V
authors.lastname: Vezzosi
authors.forename: Alberto
authors.initials: A
authors.lastname: Gulino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giannini
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bianchi
authors.forename: Francesco
authors.initials: F
authors.lastname: Sera
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D000368:Aged; D018567:Breast Neoplasms, Male / Q000453:epidemiology / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000453:epidemiology / Q000235:genetics*; D018275:Carcinoma, Lobular / Q000453:epidemiology / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010375:Pedigree