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
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 homo...
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| Format: | Article |
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Thieme Medical and Scientific Publishers Pvt. Ltd.
2017-01-01
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| Series: | South Asian Journal of Cancer |
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| Online Access: | http://journal.sajc.org/article.asp?issn=2278-330X;year=2017;volume=6;issue=3;spage=102;epage=105;aulast=Bajpai |
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| author | Jyoti Bajpai Anant Ramaswamy Arun Chandrasekharan Surya Mishra Tanuja Shet Sudeep Gupta R A Badwe |
| author_facet | Jyoti Bajpai Anant Ramaswamy Arun Chandrasekharan Surya Mishra Tanuja Shet Sudeep Gupta R A Badwe |
| author_sort | Jyoti Bajpai |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T11:13:01Z |
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| institution | Directory Open Access Journal |
| issn | 2278-330X |
| language | English |
| last_indexed | 2024-12-14T11:13:01Z |
| publishDate | 2017-01-01 |
| publisher | Thieme Medical and Scientific Publishers Pvt. Ltd. |
| record_format | Article |
| series | South Asian Journal of Cancer |
| spelling | doaj.art-bae7c7943bb2422c8997ddabb87e65ab2022-12-21T23:04:12ZengThieme Medical and Scientific Publishers Pvt. Ltd.South Asian Journal of Cancer2278-330X2017-01-016310210510.4103/sajc.sajc_113_17Activation 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 viewpointJyoti BajpaiAnant RamaswamyArun ChandrasekharanSurya MishraTanuja ShetSudeep GuptaR A BadweIntroduction: 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.http://journal.sajc.org/article.asp?issn=2278-330X;year=2017;volume=6;issue=3;spage=102;epage=105;aulast=BajpaiEverolimusmechanistic target of rapamycinmetastatic breast cancerphosphatase and tensin homolog |
| spellingShingle | Jyoti Bajpai Anant Ramaswamy Arun Chandrasekharan Surya Mishra Tanuja Shet Sudeep Gupta R A Badwe 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 South Asian Journal of Cancer Everolimus mechanistic target of rapamycin metastatic breast cancer phosphatase and tensin homolog |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Everolimus mechanistic target of rapamycin metastatic breast cancer phosphatase and tensin homolog |
| url | http://journal.sajc.org/article.asp?issn=2278-330X;year=2017;volume=6;issue=3;spage=102;epage=105;aulast=Bajpai |
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