Research Papers:

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

Piera Rizzolo, Anna Sara Navazio, Valentina Silvestri, Virginia Valentini, Veronica Zelli, Ines Zanna, Giovanna Masala, Simonetta Bianchi, Marco Scarnò, Stefania Tommasi, Domenico Palli and Laura Ottini _

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Oncotarget. 2016; 7:74097-74106. https://doi.org/10.18632/oncotarget.12272

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Piera Rizzolo1, Anna Sara Navazio1, Valentina Silvestri1, Virginia Valentini1, Veronica Zelli1, Ines Zanna2, Giovanna Masala2, Simonetta Bianchi3, Marco Scarnò4, Stefania Tommasi5, Domenico Palli2, Laura Ottini1

1Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy

2Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy

3Division of Pathological Anatomy, Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy

4CINECA (Inter University Consortium for Super Computing), Rome, Italy

5Molecular Genetics Laboratory, Istituto Tumori “Giovanni Paolo II”, Bari, Italy

Correspondence to:

Laura Ottini, email: [email protected]

Keywords: male breast cancer, somatic mutations, gene copy number variation, germ-line BRCA1/2 mutations, oncogenes

Received: July 02, 2016     Accepted: September 16, 2016     Published: September 27, 2016


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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