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Frequency of germline DNA genetic findings in an unselected prospective cohort of triple-negative breast cancer patients participating in a platinum-based neoadjuvant chemotherapy trial

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An Erratum to this article was published on 18 July 2017

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Abstract

We describe the status and frequency of germline DNA genetic findings in an unselected prospective cohort of triple negative breast cancer patients participating in a platinum-based neoadjuvant chemotherapy trial. Study population includes 124 consecutive patients with stage II-III TNBC from a trial exploring the antitumor activity of neoadjuvant carboplatin/docetaxel chemotherapy enrolled between 2012 and March 2015, to determine the frequency of germline DNA genetic mutations. 17.1 % of the patients with germline DNA tested had deleterious mutations in any of the analyzed genes (12.38 % in BRCA1, 1.9 % in BRCA2 and BARD1 and 0.95 % in RAD51D). Attending the intrinsic subtype, all the BRCA1/2 carriers tested had basal-like subtype. Among wild-type (WT) patients, 70.11 % had basal subtype, 16.09 % HER2 enriched, 1.15 % Luminal B, and 4.60 % Normal-like. Mean age at diagnosis was significantly lower in mutation-carriers compared with no carriers (43.72 vs 53.10, p = 0.004). 3 BRCA1/2 carriers were detected between 51 and 60 years, and only one deleterious mutation (BARD1) over 60 years. A positive familiar history of breast and ovarian cancer was more frequent in patients with deleterious mutations (39.39 vs 17.94 %, p = 0.043). Our study confirms the prevalence of BRCA1/2 mutations in TNBC patients. TNBC should therefore be considered by itself as a criterion for BRCA1/2 genetic testing. Determination of other breast cancer predisposition genes implicated in homologous recombination should also be discussed in this population. However, no definitive conclusions can be reached due to the low prevalence and the uncertain clinical impact of most of the genes included.

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Change history

  • 18 July 2017

    An erratum to this article has been published.

Abbreviations

BC:

Breast cancer

ER:

Estrogen receptor

FFPE:

Formalin-fixed, paraffin-embedded

gDNA:

Genomic DNA

HER2:

Human epidermal growth factor receptor 2

HR:

Homologous recombination

PR:

Progesterone receptor

TNBC:

Triple-negative breast cancer

VUS:

Variants of unknown significance

WT:

Wild-type

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Acknowledgments

This work was partially supported by the Ministry of Economy and Competitiveness ISCIII-FIS grants PI12/02684, and RD12/0036/0076, co-financed by ERDF (FEDER) Funds from the European Commission, “A way of making Europe.”

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    Authors and Affiliations

    1. Medical Oncology Service, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain

      Milagros González-Rivera, Miriam Lobo, Sara López-Tarruella, Yolanda Jerez, María del Monte-Millán, Tatiana Massarrah, Rocío Ramos-Medina, Inmaculada Ocaña, Antoni Picornell, Iván Márquez-Rodas & Miguel Martin

    2. Medical Genetics Unit, Sistemas Genómicos SA, Valencia, Spain

      Sonia Santillán Garzón & Lucía Pérez-Carbornero

    3. Medical Oncology Service, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, Spain

      José A. García-Saenz & Fernando Moreno

    4. Instituto Nacional de Enfermedades Neoplásicas (I.N.E.N.), Lima, Peru

      Henry Gómez & Hugo Fuentes

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    1. Milagros González-Rivera
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    Correspondence to Milagros González-Rivera or Miriam Lobo.

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    Ethical approval

    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was performed in accordance with the Declaration of Helsinki, approved by the ethics committees at all participating institutions and the Spanish Health Authority (Ethical Committee reference Area 1-Hospital General Universitario Gregorio Marañón).

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    The authors declare that they have no conflict of interest.

    Informed consent

    It was registered at www.clinicaltrials.gov (identifier code: NCT 01560663). The patients were diagnosed at any of the participant academic institutions including several hospitals from Spain and Peru. Informed consent was obtained from all individual participants included in this study.

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    Milagros González-Rivera and Miriam Lobo have contributed equally to this work and should be considered as first authors as equal.

    An erratum to this article is available at https://doi.org/10.1007/s10549-017-4396-0.

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    González-Rivera, M., Lobo, M., López-Tarruella, S. et al. Frequency of germline DNA genetic findings in an unselected prospective cohort of triple-negative breast cancer patients participating in a platinum-based neoadjuvant chemotherapy trial. Breast Cancer Res Treat 156, 507–515 (2016). https://doi.org/10.1007/s10549-016-3792-1

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