c-MET as a Potential Resistance Mechanism to Everolimus in Breast Cancer: From a Case Report to Patient Cohort Analysis.
Target Oncol
; 15(1): 139-146, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-32020516
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Proteínas Proto-Oncogênicas c-met
/
Everolimo
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Female
/
Humans
Idioma:
En
Revista:
Target Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Bélgica