Breast Cancer Research and Treatment

, Volume 134, Issue 1, pp 353–362

Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study

Authors

  • Florentia Fostira
    • Molecular Diagnostics Laboratory, I/R-RPNational Center for Scientific Research “Demokritos”
  • Marianthi Tsitlaidou
    • Molecular Diagnostics Laboratory, I/R-RPNational Center for Scientific Research “Demokritos”
  • Christos Papadimitriou
    • Department of Clinical Therapeutics“Alexandra” Hospital, University of Athens School of Medicine
  • Maroulio Pertesi
    • Molecular Diagnostics Laboratory, I/R-RPNational Center for Scientific Research “Demokritos”
  • Eleni Timotheadou
    • Department of Medical Oncology“Papageorgiou” Hospital, Aristotle University of Thessaloniki School of Medicine
  • Alexandra V. Stavropoulou
    • Molecular Diagnostics Laboratory, I/R-RPNational Center for Scientific Research “Demokritos”
  • Stavros Glentis
    • Molecular Diagnostics Laboratory, I/R-RPNational Center for Scientific Research “Demokritos”
  • Evangelos Bournakis
    • Department of Clinical Therapeutics“Alexandra” Hospital, University of Athens School of Medicine
  • Mattheos Bobos
    • Laboratory of Molecular Oncology, Hellenic Foundation for Cancer ResearchAristotle University of Thessaloniki School of Medicine
  • Dimitrios Pectasides
    • Oncology Section, Second Department of Internal Medicine“Hippokration” Hospital
  • Pavlos Papakostas
    • Department of Medical Oncology“Hippokration” Hospital
  • George Pentheroudakis
    • Department of Medical OncologyIoannina University Hospital
  • Helen Gogas
    • First Department of Medicine“Laiko” General Hospital, University of Athens, Medical School
  • Pantelis Skarlos
    • Department of Radiotherapy“Agios Savvas” Cancer Hospital
  • Epaminontas Samantas
    • Third Department of Medical Oncology“Agii Anargiri” Cancer Hospital
  • Dimitrios Bafaloukos
    • First Department of Medical Oncology“Metropolitan” Hospital
  • Paris A. Kosmidis
    • Second Department of Medical OncologyHygeia Hospital
  • Angelos Koutras
    • Department of Medicine, Division of OncologyUniversity Hospital, University of Patras Medical School
  • Drakoulis Yannoukakos
    • Molecular Diagnostics Laboratory, I/R-RPNational Center for Scientific Research “Demokritos”
    • Molecular Diagnostics Laboratory, I/R-RPNational Center for Scientific Research “Demokritos”
  • George Fountzilas
    • Department of Medical Oncology“Papageorgiou” Hospital, Aristotle University of Thessaloniki School of Medicine
Epidemiology

DOI: 10.1007/s10549-012-2021-9

Cite this article as:
Fostira, F., Tsitlaidou, M., Papadimitriou, C. et al. Breast Cancer Res Treat (2012) 134: 353. doi:10.1007/s10549-012-2021-9

Abstract

In spite the close association of the triple-negative breast cancer immunophenotype with hereditary breast cancers and the BRCA1 pathway, there is a lack of population studies that determine the frequency of BRCA1 mutations among triple-negative breast cancer patients. To address this, we have screened a large sample of 403 women diagnosed with triple-negative invasive breast cancer, independently of their age or family history, for germline BRCA1 mutations. Median age at diagnosis was 50 years (range 20–83). The overall prevalence of triple-negative cases among the initial patient group with invasive breast cancer was 8 %. BRCA1 was screened by direct DNA sequencing in all patients, including all exons where a mutation was previously found in the Greek population (exons 5, 11, 12, 16, 20, 21, 22, 23, 24–77 % of the BRCA1 coding region), including diagnostic PCRs to detect the three Greek founder large genomic rearrangements. Sixty-five deleterious BRCA1 mutations were identified among the 403 triple-negative breast cancer patients (16 %). Median age of onset for mutation carriers was 39 years. Among a total of 106 women with early-onset triple-negative breast cancer (<40 years), 38 (36 %) had a BRCA1 mutation, while 27 % of women with triple-negative breast cancer diagnosed before 50 years (56/208) had a BRCA1 mutation. A mutation was found in 48 % (50/105) of the triple-negative breast cancer patients with family history of breast or ovarian cancer. It is noteworthy, however, that of the 65 carriers, 15 (23 %) had no reported family history of related cancers. All but one of the carriers had grade III tumors (98 %). These results indicate that women with early-onset triple-negative breast cancer, and ideally all triple-negative breast cancer patients, are candidates for BRCA1 genetic testing even in the absence of a family history of breast or ovarian cancer.

Keywords

Triple-negative breast cancerBRCA1Hereditary breast–ovarian cancerGenetic testing

Abbreviations

ER

Estrogen receptor

PR

Progesterone receptor

HER2

Human epidermal growth factor receptor 2

PCR

Polymerase chain reaction

CI

Confidence interval

IHC

Immunohistochemistry

FISH

Fluorescence in situ hybridization

CISH

Chromogenic in situ hybridization

UV

Ultraviolet

PARP

Poly(ADP-ribose) polymerase

Copyright information

© Springer Science+Business Media, LLC. 2012