title: Somatic alterations of targetable oncogenes are frequently observed in BRCA1/2 mutation negative male breast cancers.
abstract: 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.
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Piera
authors.initials: P
authors.lastname: Rizzolo
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Anna Sara
authors.initials: AS
authors.lastname: Navazio
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Silvestri
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Valentini
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Zelli
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy.
authors.forename: Ines
authors.initials: I
authors.lastname: Zanna
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.affiliation: Division of Pathological Anatomy, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bianchi
authors.affiliation: CINECA (Inter University Consortium for Super Computing), Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Scarnò
authors.affiliation: Molecular Genetics Laboratory, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Tommasi
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ottini
mesh_terms: D001483:Base Sequence; D018567:Breast Neoplasms, Male / Q000235:genetics* / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics; D056915:DNA Copy Number Variations; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D009857:Oncogenes
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human
keywords: gene copy number variation; germ-line BRCA1/2 mutations; male breast cancer; oncogenes; somatic mutations