Abstract
PurposeTo analyze the prevalence of pathogenic/likely pathogenic variants (P/LPVs) in BRCA1 and BRCA2 genes in the largest cohort of Slovenian male breast cancer (MBC) patients to date and to explore a possible correlation between the Slovenian founder variant BRCA2:c.7806-2A > G and predisposition to MBC.MethodsWe performed a retrospective analysis of 81 MBC cases who underwent genetic counseling and/or testing between January 1999 and May 2020. To explore a possible genotype–phenotype correlation, we performed additional analyses of 203 unrelated families with P/LPVs in BRCA2 and 177 cases of female breast cancer (FBC) in carriers of P/LPVs in BRCA2.ResultsDetection rate of P/LPVs in the BRCA1 and BRCA2 genes was 24.7% (20/81) with 95% of them in BRCA2 gene. The only two recurrent P/LPVs were BRCA2:c.7806-2A > G and BRCA2:c.3975_3978dupTGCT (9 and 5 MBC cases, respectively). In families with BRCA2:c.7806-2A > G, the incidence of MBC cases was higher compared to families with other P/LPVs in BRCA2; however, the difference did not reach statistical significance (17.8% vs. 8.9%, p = 0.105). BRCA2:c.7806-2A > G was detected in both families with multiple cases of MBC. This splice-site variant represented a significantly higher proportion of all BRCA2 P/LPVs detected in MBC carriers compared to FBC carriers (47.4% vs. 26%, p = 0.049).ConclusionWe observed a high mutation detection rate and conclude this may be due to the prevalent BRCA2:c.7806-2A > G variant in Slovenia. Our results indicate a possible association between this variant and higher risk of breast cancer in males compared to other identified P/LPVs in BRCA2.
Highlights
IntroductionMale breast cancer (MBC) is a rare disease, comprising up to 1% of all breast cancers and up to 1% of all cancers in males [1,2,3]
Genetic testing is recommended for all Male breast cancer (MBC) patients in order to guide screening recommendations for other types of cancer and to identify other family members at risk [1, 7], as well as for treatment with PARP inhibitors in metastatic settings according to the American Society of Clinical Oncology 2020 guidelines [8]
We identified 81 MBC cases from 80 unrelated families who underwent genetic counseling and/or testing at our Institute between January 1999 and May 2020
Summary
Male breast cancer (MBC) is a rare disease, comprising up to 1% of all breast cancers and up to 1% of all cancers in males [1,2,3]. Environmental, hormonal, and genetic factors have been associated with MBC [2, 6]. Slovenia factors, mutations in BRCA1 and, especially, BRCA2 genes are the most clearly established predispositions [2]. In 2008, Besic together with members of our group published first results of genetic testing in a small cohort of 25 Slovenian MBC patients and reported a high prevalence of 16% of pathogenic/likely pathogenic variants (P/LPVs) in BRCA2 [9]. In three out of four MBC carriers of P/LPVs in BRCA2, the highly recurrent Slovenian founder splice-site variant BRCA2:c.7806-2A > G (formerly known as IVS162A > G) was detected [10, 11]. A group from Aviano, Italy, reported this variant as recurrent in northeast part of
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