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Somatic alterations of targetable oncogenes are frequently observed in BRCA1/2 mutation negative male breast cancers.

Oncotarget 2016 November 9
Male breast cancer (MBC) is a rare disease. Due to its rarity, MBC research and clinical approach are mostly based upon data derived from its largely known female counterpart. We aimed at investigating whether MBC cases harbor somatic alterations of genes known as prognostic biomarkers and molecular therapeutic targets in female breast cancer.We examined 103 MBC cases, all characterized for germ-line BRCA1/2 mutations, for somatic alterations in PIK3CA, EGFR, ESR1 and CCND1 genes.Pathogenic mutations of PIK3CA were detected in 2% of MBCs. No pathogenic mutations were identified in ESR1 and EGFR. Gene copy number variations (CNVs) analysis showed amplification of PIK3CA in 8.1%, EGFR in 6.8% and CCND1 in 16% of MBCs, whereas deletion of ESR1 was detected in 15% of MBCs. Somatic mutations and gene amplification were found only in BRCA1/2 mutation negative MBCs.Significant associations emerged between EGFR amplification and large tumor size (T4), ER-negative and HER2-positive status, between CCND1 amplification and HER2-positive and MIB1-positive status, and between ESR1 deletion and ER-negative status.Our results show that amplification of targetable oncogenes is frequent in BRCA1/2 mutation negative MBCs and may identify MBC subsets characterized by aggressive phenotype that may benefit from potential targeted therapeutic approaches.

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