Priority Research Papers:
Kinetics, prognostic and predictive values of ESR1 circulating mutations in metastatic breast cancer patients progressing on aromatase inhibitor
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Florian Clatot1,2,3, Anne Perdrix3,4, Laetitia Augusto1, Ludivine Beaussire3,5, Julien Delacour3,5, Céline Calbrix4, David Sefrioui3,5,6, Pierre-Julien Viailly2, Michael Bubenheim7, Cristian Moldovan1, Cristina Alexandru1, Isabelle Tennevet1, Olivier Rigal1, Cécile Guillemet1, Marianne Leheurteur1, Sophie Gouérant1, Camille Petrau1,3, Jean-Christophe Théry1,5, Jean-Michel Picquenot1,2,4, Corinne Veyret1, Thierry Frébourg5, Fabrice Jardin2, Nasrin Sarafan-Vasseur3,5,* and Frédéric Di Fiore1,3,5,6,*
1 Department of Medical Oncology, Henri Becquerel Centre, Rouen, France
2 INSERM U918, Henri Becquerel Centre, Rouen, France
3 EquIpe de Recherche en Oncologie, Rouen, France
4 Department of Biopathology, Henri Becquerel Centre, Rouen, France
5 INSERM U1079, Faculty of medecine, Rouen, France
6 Department of Gastroenterology, Rouen University Hospital, Rouen, France
7 Department of Biostatistics, Rouen University Hospital, Rouen, France
* These authors have contributed equally to the work
Florian Clatot, email:
Keywords: ESR1 mutation, digital PCR, breast cancer, aromatase inhibitor, kinetics
Received: October 12, 2016 Accepted: October 24, 2016 Published: October 27, 2016
Purpose: To assess the prognostic and predictive value of circulating ESR1 mutation and its kinetics before and after progression on aromatase inhibitor (AI) treatment.
Patients and methods: 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.
Results: 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.
Conclusion: 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.
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