c-MET as a Potential Resistance Mechanism to Everolimus in Breast Cancer: From a Case Report to Patient Cohort Analysis
(2020) Targeted Oncology — Vol. 15, n° 1, p. 139-146 (2020)
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- Abstract
- Background We describe in a patient with breast cancer the change in c-MET expression during everolimus treatment, opening a better understanding of the resistance to everolimus and a role for cabozantinib. Objective The objective of this study was to evaluate c-MET as a potential predictive biomarker for everolimus efficacy in breast cancer. Methods We first selected a patient with breast cancer with a long-lasting response to everolimus and retrospectively profiled biopsies that were taken before everolimus initiation (Biopsy 1) and at progression on everolimus (Biopsy 2) using amplicon sequencing and immunohistochemistry. We then retrospectively evaluated c-MET expression in a cohort of patients with breast cancer treated with everolimus. Results While not expressed in Biopsy 1, c-MET was highly expressed in Biopsy 2, suggesting a role for c-MET in breast cancer progression. Cabozantinib resulted in a rapid radiological response in this patient. Twenty-nine patients were included (12 c-MET-positive and 17 c-MET-negative patients) in the second part of the study. Baseline c-MET expression was associated with higher tumor grade, higher frequency of visceral metastases, and lower endocrine sensitivity. The c-MET-positive patients presented with a shorter progression-free survival (6.1 vs 10.5 months, respectively; p = 0.002) and a lower response rate (0% vs 12%) to everolimus, compared with c-MET-negative patients. Conclusions c-MET could play a role in the resistance to everolimus and its inhibition should be evaluated in breast cancer.
- Affiliations
Hopital de Jolimont, Belgium Medical Oncology Unit Hopital de Jolimont, Belgium Anatomopathology Unit Rue Louis Breguet 1, 6041 Gosselies, Belgium OncoDNA
Citations
Van Den Bossche, V., Jadot, G., Grisay, G., Pierrard, J., Honoré, N., Petit, B., Augusto, D., Sauvage, S., Laes, J.-F., & Seront, E. (2020). c-MET as a Potential Resistance Mechanism to Everolimus in Breast Cancer: From a Case Report to Patient Cohort Analysis. Targeted Oncology, 15(1), 139-146. https://doi.org/10.1007/s11523-020-00704-2 (Original work published 2020)