Insight into genetic susceptibility to male breast cancer by multigene panel testing: Results from a multicenter study in Italy

Piera Rizzolo, Veronica Zelli, Valentina Silvestri, Virginia Valentini, Ines Zanna, Simonetta Bianchi, Giovanna Masala, Alessandro Mauro Spinelli, Maria Grazia Tibiletti, Antonio Russo, Liliana Varesco, Giuseppe Giannini, Carlo Capalbo, Daniele Calistri, Laura Cortesi, Alessandra Viel, Bernardo Bonanni, Jacopo Azzollini, Siranoush Manoukian, Marco MontagnaPaolo Peterlongo, Paolo Radice, Domenico Palli, Laura Ottini

Research output: Contribution to journalArticlepeer-review


Breast cancer (BC) in men is rare and genetic predisposition is likely to play a relevant role in its etiology. Inherited mutations in BRCA1/2 account for about 13% of all cases and additional genes that may contribute to the missing heritability need to be investigated. In our study, a well-characterized series of 523 male BC (MBC) patients from the Italian multicenter study on MBC, enriched for non-BRCA1/2 MBC cases, was screened by a multigene custom panel of 50 cancer-associated genes. The main clinical-pathologic characteristics of MBC in pathogenic variant carriers and non-carriers were also compared. BRCA1/2 pathogenic variants were detected in twenty patients, thus, a total of 503 non-BRCA1/2 MBC patients were examined in our study. Twenty-seven of the non-BRCA1/2 MBC patients were carriers of germline pathogenic variants in other genes, including two APC p.Ile1307Lys variant carriers and one MUTYH biallelic variant carrier. PALB2 was the most frequently altered gene (1.2%) and PALB2 pathogenic variants were significantly associated with high risk of MBC. Non-BRCA1/2 pathogenic variant carriers were more likely to have personal (p = 0.0005) and family (p = 0.007) history of cancer. Results of our study support a central role of PALB2 in MBC susceptibility and show a low impact of CHEK2 on MBC predisposition in the Italian population. Overall, our data indicate that a multigene testing approach may benefit from appropriately selected patients with implications for clinical management and counseling of MBC patients and their family members.

Original languageEnglish
Pages (from-to)390-400
Number of pages11
JournalInternational Journal of Cancer
Issue number2
Publication statusPublished - Jul 15 2019


  • BRCA1/2
  • cancer susceptibility genes
  • germline mutations
  • male breast cancer
  • multigene panel testing

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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