Priority Research Papers:
Kinetics, prognostic and predictive values of ESR1 circulating mutations in metastatic breast cancer patients progressing on aromatase inhibitor
Metrics: PDF 1618 views | HTML 1918 views | ?
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.