Epidemiology

Breast Cancer Research and Treatment

, Volume 134, Issue 1, pp 353-362

First online:

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

  • Florentia FostiraAffiliated withMolecular Diagnostics Laboratory, I/R-RP, National Center for Scientific Research “Demokritos”
  • , Marianthi TsitlaidouAffiliated withMolecular Diagnostics Laboratory, I/R-RP, National Center for Scientific Research “Demokritos”
  • , Christos PapadimitriouAffiliated withDepartment of Clinical Therapeutics, “Alexandra” Hospital, University of Athens School of Medicine
  • , Maroulio PertesiAffiliated withMolecular Diagnostics Laboratory, I/R-RP, National Center for Scientific Research “Demokritos”
  • , Eleni TimotheadouAffiliated withDepartment of Medical Oncology, “Papageorgiou” Hospital, Aristotle University of Thessaloniki School of Medicine
  • , Alexandra V. StavropoulouAffiliated withMolecular Diagnostics Laboratory, I/R-RP, National Center for Scientific Research “Demokritos”
  • , Stavros GlentisAffiliated withMolecular Diagnostics Laboratory, I/R-RP, National Center for Scientific Research “Demokritos”
  • , Evangelos BournakisAffiliated withDepartment of Clinical Therapeutics, “Alexandra” Hospital, University of Athens School of Medicine
  • , Mattheos BobosAffiliated withLaboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine
    • , Dimitrios PectasidesAffiliated withOncology Section, Second Department of Internal Medicine, “Hippokration” Hospital
    • , Pavlos PapakostasAffiliated withDepartment of Medical Oncology, “Hippokration” Hospital
    • , George PentheroudakisAffiliated withDepartment of Medical Oncology, Ioannina University Hospital
    • , Helen GogasAffiliated withFirst Department of Medicine, “Laiko” General Hospital, University of Athens, Medical School
    • , Pantelis SkarlosAffiliated withDepartment of Radiotherapy, “Agios Savvas” Cancer Hospital
    • , Epaminontas SamantasAffiliated withThird Department of Medical Oncology, “Agii Anargiri” Cancer Hospital
    • , Dimitrios BafaloukosAffiliated withFirst Department of Medical Oncology, “Metropolitan” Hospital
    • , Paris A. KosmidisAffiliated withSecond Department of Medical Oncology, Hygeia Hospital
    • , Angelos KoutrasAffiliated withDepartment of Medicine, Division of Oncology, University Hospital, University of Patras Medical School
    • , Drakoulis YannoukakosAffiliated withMolecular Diagnostics Laboratory, I/R-RP, National Center for Scientific Research “Demokritos”
    • , Irene KonstantopoulouAffiliated withMolecular Diagnostics Laboratory, I/R-RP, National Center for Scientific Research “Demokritos” Email author 
    • , George FountzilasAffiliated withDepartment of Medical Oncology, “Papageorgiou” Hospital, Aristotle University of Thessaloniki School of Medicine

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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 cancer BRCA1 Hereditary breast–ovarian cancer Genetic testing