Abstract | 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.
|
Authors | Florian Clatot, Anne Perdrix, Laetitia Augusto, Ludivine Beaussire, Julien Delacour, Céline Calbrix, David Sefrioui, Pierre-Julien Viailly, Michael Bubenheim, Cristian Moldovan, Cristina Alexandru, Isabelle Tennevet, Olivier Rigal, Cécile Guillemet, Marianne Leheurteur, Sophie Gouérant, Camille Petrau, Jean-Christophe Théry, Jean-Michel Picquenot, Corinne Veyret, Thierry Frébourg, Fabrice Jardin, Nasrin Sarafan-Vasseur, Frédéric Di Fiore |
Journal | Oncotarget
(Oncotarget)
Vol. 7
Issue 46
Pg. 74448-74459
(11 15 2016)
ISSN: 1949-2553 [Electronic] United States |
PMID | 27801670
(Publication Type: Journal Article)
|
Chemical References |
- Aromatase Inhibitors
- Biomarkers, Tumor
- DNA, Neoplasm
- ESR1 protein, human
- Estrogen Receptor alpha
|
Topics |
- Aromatase Inhibitors
(therapeutic use)
- Biomarkers, Tumor
- Breast Neoplasms
(diagnosis, drug therapy, genetics, mortality)
- DNA, Neoplasm
- Disease Progression
- Estrogen Receptor alpha
(genetics)
- Female
- Follow-Up Studies
- Humans
- Mutation
- Neoplasm Metastasis
- Prognosis
- Retrospective Studies
- Risk Factors
- Survival Analysis
|