Activation of phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin pathway and response to everolimus in endocrine receptor‑positive metastatic breast cancer – A retrospective pilot analysis and viewpoint

Jyoti Bajpai; Anant Ramaswamy; Arun Chandrasekharan; Surya Mishra; Tanuja Shet; Sudeep Gupta; R. A. Badwe

doi:10.4103/sajc.sajc_113_17

South Asian Journal of Cancer, Table of Contents

CC BY-NC-ND 4.0 · South Asian J Cancer 2017; 06(03): 102-105
DOI: 10.4103/sajc.sajc_113_17

ORIGINAL ARTICLE : Breast Cancer

Activation of phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin pathway and response to everolimus in endocrine receptor‑positive metastatic breast cancer – A retrospective pilot analysis and viewpoint

Authors

Jyoti Bajpai

Deparment of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
Anant Ramaswamy

Deparment of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
Arun Chandrasekharan

Deparment of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
Surya Mishra

Deparment of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
Tanuja Shet

Deparment of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
Sudeep Gupta

Deparment of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
R. A. Badwe

Deparment of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra

Abstract

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Abstract

Introduction: Biomarkers predictive of response to mechanistic target of rapamycin (mTOR) inhibitor, everolimus, in endocrine receptor (ER)-positive metastatic breast cancer (MBC) are a work in progress. We evaluated the feasibility of directly measuring mTOR activity and phosphatase and tensin homolog (PTEN) expression and correlating their expression with response and survival. Materials and Methods: MBC patients who received everolimus with endocrine therapy (ET) after progression on an aromatase inhibitor and had adequate tissue preservation for estimation of mTOR activity and PTEN expression were selected for analysis from a prospectively maintained database. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan–Meier method, and correlation between mTOR activity and PTEN expression with survival was done by log-rank test. Results: Thirteen ER-positive MBC patients were available for analysis. PTEN expression was lost in 11/13 (84.6%) patients and retained in 2/13 patients (15.4%). mTOR activity was absent in four patients (30.7%), weak in six patients (46.1%), and moderate in 3 patients (23.2%). Median PFS for the entire population was 2.5 months while median OS was not reached. Patients with an absent mTOR activity showed a longer PFS (5 vs. 1.5 vs. 2 months) than those with weak and moderate activity, respectively (P = 0.043). There was no correlation between loss of PTEN expression and PFS. Conclusions: Measurement of direct mTOR activity in patients with MBC receiving everolimus/ET combination appears feasible. Absent mTOR activity may predict for longer PFS with everolimus-ET combination and requires further study.

Key words

Everolimus - mechanistic target of rapamycin - metastatic breast cancer - phosphatase and tensin homolog

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References

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