PLoS Medicine (Dec 2016)

Mutational Profile of Metastatic Breast Cancers: A Retrospective Analysis.

  • Celine Lefebvre,
  • Thomas Bachelot,
  • Thomas Filleron,
  • Marion Pedrero,
  • Mario Campone,
  • Jean-Charles Soria,
  • Christophe Massard,
  • Christelle Lévy,
  • Monica Arnedos,
  • Magali Lacroix-Triki,
  • Julie Garrabey,
  • Yannick Boursin,
  • Marc Deloger,
  • Yu Fu,
  • Frédéric Commo,
  • Véronique Scott,
  • Ludovic Lacroix,
  • Maria Vittoria Dieci,
  • Maud Kamal,
  • Véronique Diéras,
  • Anthony Gonçalves,
  • Jean-Marc Ferrerro,
  • Gilles Romieu,
  • Laurence Vanlemmens,
  • Marie-Ange Mouret Reynier,
  • Jean-Christophe Théry,
  • Fanny Le Du,
  • Séverine Guiu,
  • Florence Dalenc,
  • Gilles Clapisson,
  • Hervé Bonnefoi,
  • Marta Jimenez,
  • Christophe Le Tourneau,
  • Fabrice André

DOI
https://doi.org/10.1371/journal.pmed.1002201
Journal volume & issue
Vol. 13, no. 12
p. e1002201

Abstract

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BackgroundMajor advances have been achieved in the characterization of early breast cancer (eBC) genomic profiles. Metastatic breast cancer (mBC) is associated with poor outcomes, yet limited information is available on the genomic profile of this disease. This study aims to decipher mutational profiles of mBC using next-generation sequencing.Methods and findingsWhole-exome sequencing was performed on 216 tumor-blood pairs from mBC patients who underwent a biopsy in the context of the SAFIR01, SAFIR02, SHIVA, or Molecular Screening for Cancer Treatment Optimization (MOSCATO) prospective trials. Mutational profiles from 772 primary breast tumors from The Cancer Genome Atlas (TCGA) were used as a reference for comparing primary and mBC mutational profiles. Twelve genes (TP53, PIK3CA, GATA3, ESR1, MAP3K1, CDH1, AKT1, MAP2K4, RB1, PTEN, CBFB, and CDKN2A) were identified as significantly mutated in mBC (false discovery rate [FDR] ConclusionsThis work reports the results of the analysis of the first large-scale study on mutation profiles of mBC. This study revealed genomic alterations and mutational signatures involved in the resistance to therapies, including actionable mutations.