Breast Cancer Research and Treatment

, Volume 169, Issue 1, pp 105–113 | Cite as

Germline deleterious mutations in genes other than BRCA2 are infrequent in male breast cancer

  • Florentia Fostira
  • Emmanouil Saloustros
  • Paraskevi Apostolou
  • Andromahi Vagena
  • Despoina Kalfakakou
  • Davide Mauri
  • Dimitrios Tryfonopoulos
  • Vassileios Georgoulias
  • Drakoulis Yannoukakos
  • Georgios Fountzilas
  • Irene Konstantopoulou
Epidemiology

Abstract

Purpose

Male breast cancer (MBC) is a rare cancer entity, with mutations in BRCA1 and BRCA2 genes accounting for ~ 10% of patients. Multiple-gene sequencing has already entered clinical practice for female breast cancer, whereas the performance of panel testing in MBC has not been studied extensively. Therefore, the aim of this study was to evaluate the clinical utility of panel testing for MBC, by the largest gene panel used so far, through investigation of patients deriving from a population with known founder effects.

Methods

Genomic DNA from one hundred and two Greek MBC patients, unselected for age and family history, was used to prepare libraries which capture the entire coding regions of 94 cancer genes.

Results

Loss-of-function (LoF) mutations were found in 12.7% of the cases, distributed in six genes: BRCA2, ATM, BRCA1, CHEK2, PMS2, and FANCL. BRCA2 mutations were the most frequent, followed by ATM mutations, accounting for 6.9 and 2%, respectively, while mutations in other genes were detected in single cases. Age at diagnosis or family history was not predictive of mutation status. Beyond mutations in established breast cancer predisposing genes, LoF mutations in PMS2 and FANCL among MBC patients are reported here for the first time.

Conclusions

Our findings, using the largest gene panel for MBC patients so far, indicate that BRCA testing should be the primary concern for MBC patients. Until sufficient evidence arises from larger studies, multiple-gene panels may be of limited benefit for MBC and their families, at least for MBC patients of specific descent.

Keywords

Male breast cancer BRCA1 BRCA2 NGS Hereditary cancer 

Notes

Acknowledgements

We are indebted to the patients who participated in our research.

Compliance with ethical standards

Conflict of interest

The authors have no disclosures/conflict of interest to declare.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Florentia Fostira
    • 1
  • Emmanouil Saloustros
    • 2
  • Paraskevi Apostolou
    • 1
  • Andromahi Vagena
    • 1
  • Despoina Kalfakakou
    • 1
  • Davide Mauri
    • 3
  • Dimitrios Tryfonopoulos
    • 4
  • Vassileios Georgoulias
    • 5
  • Drakoulis Yannoukakos
    • 1
  • Georgios Fountzilas
    • 6
  • Irene Konstantopoulou
    • 1
  1. 1.Molecular Diagnostics Laboratory, INRaSTESNational Centre for Scientific Research ‘Demokritos’AthensGreece
  2. 2.Oncology UnitGeneral Hospital of Heraklion ‘Venizelio-Pananio’HeraklionGreece
  3. 3.General Hospital of LamiaLamiaGreece
  4. 4.Second Department of Medical Oncology‘Agios Savvas’ Anticancer HospitalAthensGreece
  5. 5.Department of Medical OncologyUniversity Hospital of HeraklionHeraklionGreece
  6. 6.Aristotle University of Thessaloniki School of MedicineThessalonikiGreece

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