Abstract
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 language | English |
|---|---|
| Pages (from-to) | 390-400 |
| Number of pages | 11 |
| Journal | International Journal of Cancer |
| Volume | 145 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jul 15 2019 |
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Keywords
- BRCA1/2
- cancer susceptibility genes
- germline mutations
- male breast cancer
- multigene panel testing
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Insight into genetic susceptibility to male breast cancer by multigene panel testing : Results from a multicenter study in Italy. / Rizzolo, Piera; Zelli, Veronica; Silvestri, Valentina; Valentini, Virginia; Zanna, Ines; Bianchi, Simonetta; Masala, Giovanna; Spinelli, Alessandro Mauro; Tibiletti, Maria Grazia; Russo, Antonio; Varesco, Liliana; Giannini, Giuseppe; Capalbo, Carlo; Calistri, Daniele; Cortesi, Laura; Viel, Alessandra; Bonanni, Bernardo; Azzollini, Jacopo; Manoukian, Siranoush; Montagna, Marco; Peterlongo, Paolo; Radice, Paolo; Palli, Domenico; Ottini, Laura.
In: International Journal of Cancer, Vol. 145, No. 2, 15.07.2019, p. 390-400.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Insight into genetic susceptibility to male breast cancer by multigene panel testing
T2 - Results from a multicenter study in Italy
AU - Rizzolo, Piera
AU - Zelli, Veronica
AU - Silvestri, Valentina
AU - Valentini, Virginia
AU - Zanna, Ines
AU - Bianchi, Simonetta
AU - Masala, Giovanna
AU - Spinelli, Alessandro Mauro
AU - Tibiletti, Maria Grazia
AU - Russo, Antonio
AU - Varesco, Liliana
AU - Giannini, Giuseppe
AU - Capalbo, Carlo
AU - Calistri, Daniele
AU - Cortesi, Laura
AU - Viel, Alessandra
AU - Bonanni, Bernardo
AU - Azzollini, Jacopo
AU - Manoukian, Siranoush
AU - Montagna, Marco
AU - Peterlongo, Paolo
AU - Radice, Paolo
AU - Palli, Domenico
AU - Ottini, Laura
PY - 2019/7/15
Y1 - 2019/7/15
N2 - 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.
AB - 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.
KW - BRCA1/2
KW - cancer susceptibility genes
KW - germline mutations
KW - male breast cancer
KW - multigene panel testing
UR - http://www.scopus.com/inward/record.url?scp=85060589249&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060589249&partnerID=8YFLogxK
U2 - 10.1002/ijc.32106
DO - 10.1002/ijc.32106
M3 - Article
C2 - 30613976
AN - SCOPUS:85060589249
VL - 145
SP - 390
EP - 400
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 2
ER -