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Phenotypic discordance between primary and metastatic breast cancer in the large-scale real-life multicenter French ESME cohort

  • Grinda, Thomas1
  • Joyon, Natacha1
  • Lusque, Amélie2
  • Lefèvre, Sarah1
  • Arnould, Laurent3
  • Penault-Llorca, Frédérique4
  • Macgrogan, Gaëtan5
  • Treilleux, Isabelle6
  • Vincent-Salomon, Anne7
  • Haudebourg, Juliette8
  • Maran-Gonzalez, Aurélie9
  • Charafe-Jauffret, Emmanuelle10
  • Courtinard, Coralie11
  • Franchet, Camille2
  • Verriele, Véronique12
  • Brain, Etienne13
  • Tas, Patrick14
  • Blanc-Fournier, Cécile15
  • Leroux, Agnès16
  • Loussouarn, Delphine17
  • And 7 more
  • 1 Gustave Roussy Cancer Campus, Villejuif, France , Villejuif (France)
  • 2 Institut Claudius Regaud, IUCT-Oncopôle, Toulouse, France , Toulouse (France)
  • 3 Centre GF Leclerc, Dijon, France , Dijon (France)
  • 4 Centre Jean-Perrin, Clermont-Ferrand, France , Clermont-Ferrand (France)
  • 5 Institut Bergonié, Bordeaux, France , Bordeaux (France)
  • 6 Centre Léon Bérard, Lyon, France , Lyon (France)
  • 7 Institut Curie, Paris, France , Paris (France)
  • 8 Centre Lacassagne, Nice, France , Nice (France)
  • 9 ICM, Montpellier, France , Montpellier (France)
  • 10 Institut Paoli-Calmettes, Marseille, France , Marseille (France)
  • 11 Unicancer R&D, Paris, France , Paris (France)
  • 12 Institut de Cancérologie de l’Ouest, Angers, France , Angers (France)
  • 13 Institut Curie, Saint-Cloud, France , Saint-Cloud (France)
  • 14 Atalante Pathologie, Rennes, France , Rennes (France)
  • 15 Centre François Baclesse, Caen, France , Caen (France)
  • 16 Institut de cancérologie de Lorraine, Nancy, France , Nancy (France)
  • 17 Centre hospitalo-universitaire Nantes Hotel-Dieu, Nantes, France , Nantes (France)
  • 18 Centre Henri Becquerel, Rouen, France , Rouen (France)
  • 19 Institut Godinot, Reims, France , Reims (France)
  • 20 Centre Paul Strauss, Strasbourg, France , Strasbourg (France)
Published Article
npj Breast Cancer
Nature Publishing Group UK
Publication Date
Apr 16, 2021
DOI: 10.1038/s41523-021-00252-6
Springer Nature


Expression of hormone receptor (HR) for estrogens (ER) and progesterone (PR) and HER2 remains the cornerstone to define the therapeutic strategy for breast cancer patients. We aimed to compare phenotypic profiles between matched primary and metastatic breast cancer (MBC) in the ESME database, a National real-life multicenter cohort of MBC patients. Patients with results available on both primary tumour and metastatic disease within 6 months of MBC diagnosis and before any tumour progression were eligible for the main analysis. Among the 16,703 patients included in the database, 1677 (10.0%) had available biopsy results at MBC diagnosis and on matched primary tumour. The change rate of either HR or HER2 was 27.0%. Global HR status changed (from positive = either ER or PR positive, to negative = both negative; and reverse) in 14.2% of the cases (expression loss in 72.5% and gain in 27.5%). HER2 status changed in 7.8% (amplification loss in 45.2%). The discordance rate appeared similar across different biopsy sites. Metastasis to bone, HER2+ and RH+/HER2- subtypes and previous adjuvant endocrine therapy, but not relapse interval were associated with an HR discordance in multivariable analysis. Loss of HR status was significantly associated with a risk of death (HR adjusted = 1.51, p = 0.002) while gain of HR and HER2 discordance was not. In conclusion, discordance of HR and HER2 expression between primary and metastatic breast cancer cannot be neglected. In addition, HR loss is associated with worse survival. Sampling metastatic sites is essential for treatment adjustment.

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