title: Kinetics, prognostic and predictive values of ESR1 circulating mutations in metastatic breast cancer patients progressing on aromatase inhibitor.
abstract: To assess the prognostic and predictive value of circulating ESR1 mutation and its kinetics before and after progression on aromatase inhibitor (AI) treatment.
  
  
  
  ESR1 circulating D538G and Y537S/N/C mutations were retrospectively analyzed by digital droplet PCR after first-line AI failure in patients treated consecutively from 2010 to 2012 for hormone receptor-positive metastatic breast cancer. Progression-free survival (PFS) and overall survival (OS) were analyzed according to circulating mutational status and subsequent lines of treatment. The kinetics of ESR1 mutation before (3 and 6 months) and after (3 months) AI progression were determined in the available archive plasmas.
  
  
  
  Circulating ESR1 mutations were found at AI progression in 44/144 patients included (30.6%). Median follow-up from AI initiation was 40 months (range 4-94). The median OS was decreased in patients with circulating ESR1 mutation than in patients without mutation (15.5 versus 23.8 months, P=0.0006). The median PFS was also significantly decreased in patients with ESR1 mutation than in patients without mutation (5.9 vs 7 months, P=0.002). After AI failure, there was no difference in outcome for patients receiving chemotherapy (n = 58) versus non-AI endocrine therapy (n=51) in patients with and without ESR1 mutation. ESR1 circulating mutations were detectable in 75% of all cases before AI progression, whereas the kinetics 3 months after progression did not correlate with outcome.
  
  
  
  ESR1 circulating mutations are independent risk factors for poor outcome after AI failure, and are frequently detectable before clinical progression. Interventional studies based on ESR1 circulating status are warranted.
authors: Department of Medical Oncology, Henri Becquerel Centre, Rouen, France.|INSERM U918, Henri Becquerel Centre, Rouen, France.|EquIpe de Recherche en Oncologie, Rouen, France.
authors: Florian
authors: F
authors: Clatot
authors: EquIpe de Recherche en Oncologie, Rouen, France.|Department of Biopathology, Henri Becquerel Centre, Rouen, France.
authors: Anne
authors: A
authors: Perdrix
authors: Department of Medical Oncology, Henri Becquerel Centre, Rouen, France.
authors: Laetitia
authors: L
authors: Augusto
authors: EquIpe de Recherche en Oncologie, Rouen, France.|INSERM U1079, Faculty of Medecine, Rouen, France.
authors: Ludivine
authors: L
authors: Beaussire
authors: EquIpe de Recherche en Oncologie, Rouen, France.|INSERM U1079, Faculty of Medecine, Rouen, France.
authors: Julien
authors: J
authors: Delacour
authors: Department of Biopathology, Henri Becquerel Centre, Rouen, France.
authors: Céline
authors: C
authors: Calbrix
authors: EquIpe de Recherche en Oncologie, Rouen, France.|INSERM U1079, Faculty of Medecine, Rouen, France.|Department of Gastroenterology, Rouen University Hospital, Rouen, France.
authors: David
authors: D
authors: Sefrioui
authors: INSERM U918, Henri Becquerel Centre, Rouen, France.
authors: Pierre-Julien
authors: PJ
authors: Viailly
authors: Department of Biostatistics, Rouen University Hospital, Rouen, France.
authors: Michael
authors: M
authors: Bubenheim
authors: Department of Medical Oncology, Henri Becquerel Centre, Rouen, France.
authors: Cristian
authors: C
authors: Moldovan
authors: Department of Medical Oncology, Henri Becquerel Centre, Rouen, France.
authors: Cristina
authors: C
authors: Alexandru
authors: Department of Medical Oncology, Henri Becquerel Centre, Rouen, France.
authors: Isabelle
authors: I
authors: Tennevet
authors: Department of Medical Oncology, Henri Becquerel Centre, Rouen, France.
authors: Olivier
authors: O
authors: Rigal
authors: Department of Medical Oncology, Henri Becquerel Centre, Rouen, France.
authors: Cécile
authors: C
authors: Guillemet
authors: Department of Medical Oncology, Henri Becquerel Centre, Rouen, France.
authors: Marianne
authors: M
authors: Leheurteur
authors: Department of Medical Oncology, Henri Becquerel Centre, Rouen, France.
authors: Sophie
authors: S
authors: Gouérant
authors: Department of Medical Oncology, Henri Becquerel Centre, Rouen, France.|EquIpe de Recherche en Oncologie, Rouen, France.
authors: Camille
authors: C
authors: Petrau
authors: Department of Medical Oncology, Henri Becquerel Centre, Rouen, France.|INSERM U1079, Faculty of Medecine, Rouen, France.
authors: Jean-Christophe
authors: JC
authors: Théry
authors: Department of Medical Oncology, Henri Becquerel Centre, Rouen, France.|INSERM U918, Henri Becquerel Centre, Rouen, France.|Department of Biopathology, Henri Becquerel Centre, Rouen, France.
authors: Jean-Michel
authors: JM
authors: Picquenot
authors: Department of Medical Oncology, Henri Becquerel Centre, Rouen, France.
authors: Corinne
authors: C
authors: Veyret
authors: INSERM U1079, Faculty of Medecine, Rouen, France.
authors: Thierry
authors: T
authors: Frébourg
authors: INSERM U918, Henri Becquerel Centre, Rouen, France.
authors: Fabrice
authors: F
authors: Jardin
authors: EquIpe de Recherche en Oncologie, Rouen, France.|INSERM U1079, Faculty of Medecine, Rouen, France.
authors: Nasrin
authors: N
authors: Sarafan-Vasseur
authors: Department of Medical Oncology, Henri Becquerel Centre, Rouen, France.|EquIpe de Recherche en Oncologie, Rouen, France.|INSERM U1079, Faculty of Medecine, Rouen, France.|Department of Gastroenterology, Rouen University Hospital, Rouen, France.
authors: Frédéric
authors: F
authors: Di Fiore
mesh_terms: D047072:Aromatase Inhibitors / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D004273:DNA, Neoplasm; D018450:Disease Progression; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D009154:Mutation; D009362:Neoplasm Metastasis; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha
keywords: ESR1 mutation; aromatase inhibitor; breast cancer; digital PCR; kinetics