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- Molecular features of untreated breast cancer and initial metastatic event inform clinical decision-making and predict outcome: long-term results of ESOPE, a single-arm prospective multicenter study
Molecular features of untreated breast cancer and initial metastatic event inform clinical decision-making and predict outcome: long-term results of ESOPE, a single-arm prospective multicenter study
Auteurs
Céline Callens, Keltouma Driouch, Anaïs Boulai, Zakia Tariq, Aurélie Comte, Frédérique Berger, Lisa Belin, Ivan Bièche, Vincent Servois, Patricia Legoix, Virginie Bernard, Sylvain Baulande, Walid Chemlali, François-Clément Bidard, Virginie Fourchotte, Anne Vincent- Salomon, Etienne Brain, Rosette Lidereau, Thomas Bachelot, Mahasti Saghatchian, Mario Campone, Sylvie Giacchetti, Brigitte Sigal Zafrani, Paul Cottu
Résumé
Abstract
Background
Prognosis evaluation of advanced breast cancer and therapeutic strategy are mostly based on clinical features of advanced disease and molecular profiling of the primary tumor. Very few studies have evaluated the impact of metastatic subtyping during the initial metastatic event in a prospective study. The genomic landscape of metastatic breast cancer has mostly been described in very advanced, pretreated disease, limiting the findings transferability to clinical use.
Methods
We developed a multicenter, single-arm, prospective clinical trial in order to address these issues. Between November 2010 and September 2013, 123 eligible patients were included. Patients at the first, untreated metastatic event were eligible. All matched primary tumors and metastatic samples were centrally reviewed for pathological typing. Targeted and whole-exome sequencing was applied to matched pairs of frozen tissue. A multivariate overall survival analysis was performed (median follow-up 64 months).
Results
Per central review in 84 patients (out of 130), we show that luminal A breast tumors are more prone to subtype switching. By combining targeted sequencing of a 91 gene panel (
Conclusions
Profiling of the first, untreated, metastatic event of breast cancer reveals a profound heterogeneity mostly in luminal A tumors and in late metastases. Based on this profiling, we can derive information relevant to prognosis and therapeutic intervention, which support current guidelines recommending a biopsy at the first metastatic relapse.
Trial registration
The trial was registered at ClinicalTrials.gov (NCT01956552).
Membres
