Abstract
Male breast cancer (MBC) is a rare disease that represents <1 % of all breast cancers (BCs). We analyze the results of a multicenter study performed in Spanish familial MBC including family history of hereditary breast and ovarian cancer syndrome (HBOCS) and clinicopathological features. We also study the relationship between BRCA1/BRCA2 mutational status in male relatives affected with cancer (MAC) and, family history and tumor types. The study included 312 men index cases with family history of HBOCS and 61 MAC BRCA1/2 mutation-carriers. Family history, histological grade (HG), clinicopathological and immunohistochemistry data were collected. BRCA1/2 mutation analyses were performed by direct sequencing or screening methods and the large rearrangements by multiplex ligation dependent probe amplification. We found 49 mutation-carriers (15.7 %), 95.9 % with BRCA2 mutations. BRCA2 mutation-carriers were associated with families with at least one MBC and one BC in female (type II; p = 0.05). Strong association were found between the presence of pathogenic mutations in MBCs and the advanced HG (p = 0.003). c.658_659delTG, c.2808_2811delACAA, c.6275_6276delTT and c.9026_9030delATCAT were the most prevalent mutations. In 61 MAC we found 20 mutations in BRCA1 and 41 in BRCA2. For MAC we show that mutational status was differentially associated with family history (p = 0.018) and tumor type, being BRCA2 mutations linked with BC and prostatic cancer (p = 0.018). MBC caused by BRCA1/2 mutations define two types of MBCs. The most frequent caused by BRCA2 mutation linked to type II families and the rarest one attributed to BRCA1 mutation. Tumor associated with MAC suggest that only BRCA2 mutations have to do with a specific type of cancer (BC and prostatic cancer); but the linkage to tumors is questionable for BRCA1 mutations .
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Acknowledgments
All authors manifest their gratitude to the families who participated in the research studies described in this article and to the researchers José Antonio López Guerrero (IVO; Valencia) and Conxi Lázaro (Laboratori de Recerca Translacional del ICO; Hospitalet). We also would like to thank to the Health Research Institute La Fe for having granted fellowships to Rosa Murria Estal, Marta Llop García and Gema Pérez Simó which have made possible their participation in the study in the laboratory of Molecular Biology La Fe; the ICO authors wish to thank to the ICO Hereditary Cancer Program team; the Institute of Genetics and Molecular Biology of Valladolid authors wish to thank the Cancer Prevention Program of the Regional Government of Castilla y León. This study has been supported, in part, by grants from the Asociación Española Contra el Cáncer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia; Mutua Madrileña Foundation (FMMA); Spanish Association against Cancer (AECC08); FMM Foundation given to AV and the following projects: ISCIIIRETIC; RD06/0020/1051; RD12/0036/008; PI10/01422; PI10/00748; PI13/00285; 2009SGR290; RTICC 06/0020/1060; FISPI12/00070 and 10PXIB 9101297PR.
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de Juan, I., Palanca, S., Domenech, A. et al. BRCA1 and BRCA2 mutations in males with familial breast and ovarian cancer syndrome. Results of a Spanish multicenter study. Familial Cancer 14, 505–513 (2015). https://doi.org/10.1007/s10689-015-9814-z
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DOI: https://doi.org/10.1007/s10689-015-9814-z