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

  • Epidemiology
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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.

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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

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Acknowledgments

We are indebted to the patients and their families. We would like to thank Ms. Maria Malliota, Research Associate, (Department of Medical Oncology, “Papageorgiou” Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Macedonia, Greece) for her help with blood sample collection and Ms. Eneida Jaupaj (Molecular Diagnostics Laboratory, I/R-RP, National Center for Scientific Research “Demokritos”, Athens, Greece) for her help with DNA extraction. We also thank Dr. George M. Spyrou and Ms. Argyro Antaraki, biostatisticians, for their valuable contribution to the statistical analysis. F. F. acknowledges support from the Post-Graduate Fellowship Program of N.C.S.R. “Demokritos”. M. P. acknowledges support from the Graduate Fellowship Program of N.C.S.R. “Demokritos”. This study was partly supported by the Greek General Secretary for Research and Technology (GSRT) Program, Research in Excellence II, funded by 75 % from the European Union and the Operational Program “Education & Lifelong Learning” ESPA-THALIS#266 of the Ministry of Education, Lifelong Learning & Religious Affairs.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Molecular Diagnostics Laboratory, I/R-RP, National Center for Scientific Research “Demokritos”, Agia Paraskevi, 15310, Athens, Greece

    Florentia Fostira, Marianthi Tsitlaidou, Maroulio Pertesi, Alexandra V. Stavropoulou, Stavros Glentis, Drakoulis Yannoukakos & Irene Konstantopoulou

  2. Department of Clinical Therapeutics, “Alexandra” Hospital, University of Athens School of Medicine, Athens, Greece

    Christos Papadimitriou & Evangelos Bournakis

  3. Department of Medical Oncology, “Papageorgiou” Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloníki, Macedonia, Greece

    Eleni Timotheadou & George Fountzilas

  4. Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Thessaloníki, Greece

    Mattheos Bobos

  5. Oncology Section, Second Department of Internal Medicine, “Hippokration” Hospital, Athens, Greece

    Dimitrios Pectasides

  6. Department of Medical Oncology, “Hippokration” Hospital, Athens, Greece

    Pavlos Papakostas

  7. Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece

    George Pentheroudakis

  8. First Department of Medicine, “Laiko” General Hospital, University of Athens, Medical School, Athens, Greece

    Helen Gogas

  9. Department of Radiotherapy, “Agios Savvas” Cancer Hospital, Athens, Greece

    Pantelis Skarlos

  10. Third Department of Medical Oncology, “Agii Anargiri” Cancer Hospital, Athens, Greece

    Epaminontas Samantas

  11. First Department of Medical Oncology, “Metropolitan” Hospital, Athens, Greece

    Dimitrios Bafaloukos

  12. Second Department of Medical Oncology, Hygeia Hospital, Athens, Greece

    Paris A. Kosmidis

  13. Department of Medicine, Division of Oncology, University Hospital, University of Patras Medical School, Patras, Greece

    Angelos Koutras

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  1. Florentia Fostira
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  2. Marianthi Tsitlaidou
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  7. Stavros Glentis
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  8. Evangelos Bournakis
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  9. Mattheos Bobos
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  10. Dimitrios Pectasides
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Correspondence to Irene Konstantopoulou.

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Fostira, F., Tsitlaidou, M., Papadimitriou, C. et al. Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study. Breast Cancer Res Treat 134, 353–362 (2012). https://doi.org/10.1007/s10549-012-2021-9

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