Use of mTOR inhibitors in the treatment of breast cancer: an evaluation of factors that influence patient outcomes

Guy Jerusalem, Andree Rorive, Joelle Collignon Medical Oncology, CHU Sart Tilman Liege, Domaine Universitaire du Sart Tilman, Liege, Belgium Abstract: Many systemic treatment options are available for advanced breast cancer, including endocrine therapy, chemotherapy, anti-human epidermal growth fa...

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Autores principales:	Jerusalem G, Rorive A, Collignon J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/1f0e58e98d5e486282c90ca33f82886e
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spelling	oai:doaj.org-article:1f0e58e98d5e486282c90ca33f82886e2021-12-02T02:17:16ZUse of mTOR inhibitors in the treatment of breast cancer: an evaluation of factors that influence patient outcomes1179-1314https://doaj.org/article/1f0e58e98d5e486282c90ca33f82886e2014-04-01T00:00:00Zhttp://www.dovepress.com/use-of-mtor-inhibitors-in-the-treatment-of-breast-cancer-an-evaluation-a16502https://doaj.org/toc/1179-1314 Guy Jerusalem, Andree Rorive, Joelle Collignon Medical Oncology, CHU Sart Tilman Liege, Domaine Universitaire du Sart Tilman, Liege, Belgium Abstract: Many systemic treatment options are available for advanced breast cancer, including endocrine therapy, chemotherapy, anti-human epidermal growth factor receptor 2 (HER2) therapy, and other targeted agents. Recently, everolimus, a mammalian target of rapamycin (mTOR) inhibitor, combined with exemestane, an aromatase inhibitor, has been approved in Europe and the USA for patients suffering from estrogen receptor-positive, HER2-negative advanced breast cancer previously treated by a nonsteroidal aromatase inhibitor, based on the results of BOLERO-2 (Breast cancer trials of OraL EveROlimus). This study showed a statistically significant and clinically meaningful improvement in median progression-free survival. Results concerning the impact on overall survival are expected in the near future. This clinically oriented review focuses on the use of mTOR inhibitors in breast cancer. Results reported with first-generation mTOR inhibitors (ridaforolimus, temsirolimus, everolimus) are discussed. The current and potential role of mTOR inhibitors is reported according to breast cancer subtype (estrogen receptor-positive HER2-negative, triple-negative, and HER2-positive ER-positive/negative disease). Everolimus is currently being evaluated in the adjuvant setting in high-risk estrogen receptor-positive, HER2-negative early breast cancer. Continuing mTOR inhibition or alternatively administering other drugs targeting the phosphatidylinositol-3-kinase/protein kinase B-mTOR pathway after progression on treatments including an mTOR inhibitor is under evaluation. Potential biomarkers to select patients showing a more pronounced benefit are reviewed, but we are not currently using these biomarkers in routine practice. Subgroup analysis of BOLERO 2 has shown that the benefit is consistent in all subgroups and that it is impossible to select patients not benefiting from addition of everolimus to exemestane. Side effects and impact on quality of life are other important issues discussed in this review. Second-generation mTOR inhibitors and dual mTOR-phosphatidylinositol-3-kinase inhibitors are currently being evaluated in clinical trials. Keywords: breast cancer, treatment, everolimus, mTOR inhibitors, biomarkers, phosphatidylinositol-3-kinase/protein kinase B-mTOR pathwayJerusalem GRorive ACollignon JDove Medical PressarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer: Targets and Therapy, Vol 2014, Iss default, Pp 43-57 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jerusalem G Rorive A Collignon J Use of mTOR inhibitors in the treatment of breast cancer: an evaluation of factors that influence patient outcomes
description	Guy Jerusalem, Andree Rorive, Joelle Collignon Medical Oncology, CHU Sart Tilman Liege, Domaine Universitaire du Sart Tilman, Liege, Belgium Abstract: Many systemic treatment options are available for advanced breast cancer, including endocrine therapy, chemotherapy, anti-human epidermal growth factor receptor 2 (HER2) therapy, and other targeted agents. Recently, everolimus, a mammalian target of rapamycin (mTOR) inhibitor, combined with exemestane, an aromatase inhibitor, has been approved in Europe and the USA for patients suffering from estrogen receptor-positive, HER2-negative advanced breast cancer previously treated by a nonsteroidal aromatase inhibitor, based on the results of BOLERO-2 (Breast cancer trials of OraL EveROlimus). This study showed a statistically significant and clinically meaningful improvement in median progression-free survival. Results concerning the impact on overall survival are expected in the near future. This clinically oriented review focuses on the use of mTOR inhibitors in breast cancer. Results reported with first-generation mTOR inhibitors (ridaforolimus, temsirolimus, everolimus) are discussed. The current and potential role of mTOR inhibitors is reported according to breast cancer subtype (estrogen receptor-positive HER2-negative, triple-negative, and HER2-positive ER-positive/negative disease). Everolimus is currently being evaluated in the adjuvant setting in high-risk estrogen receptor-positive, HER2-negative early breast cancer. Continuing mTOR inhibition or alternatively administering other drugs targeting the phosphatidylinositol-3-kinase/protein kinase B-mTOR pathway after progression on treatments including an mTOR inhibitor is under evaluation. Potential biomarkers to select patients showing a more pronounced benefit are reviewed, but we are not currently using these biomarkers in routine practice. Subgroup analysis of BOLERO 2 has shown that the benefit is consistent in all subgroups and that it is impossible to select patients not benefiting from addition of everolimus to exemestane. Side effects and impact on quality of life are other important issues discussed in this review. Second-generation mTOR inhibitors and dual mTOR-phosphatidylinositol-3-kinase inhibitors are currently being evaluated in clinical trials. Keywords: breast cancer, treatment, everolimus, mTOR inhibitors, biomarkers, phosphatidylinositol-3-kinase/protein kinase B-mTOR pathway
format	article
author	Jerusalem G Rorive A Collignon J
author_facet	Jerusalem G Rorive A Collignon J
author_sort	Jerusalem G
title	Use of mTOR inhibitors in the treatment of breast cancer: an evaluation of factors that influence patient outcomes
title_short	Use of mTOR inhibitors in the treatment of breast cancer: an evaluation of factors that influence patient outcomes
title_full	Use of mTOR inhibitors in the treatment of breast cancer: an evaluation of factors that influence patient outcomes
title_fullStr	Use of mTOR inhibitors in the treatment of breast cancer: an evaluation of factors that influence patient outcomes
title_full_unstemmed	Use of mTOR inhibitors in the treatment of breast cancer: an evaluation of factors that influence patient outcomes
title_sort	use of mtor inhibitors in the treatment of breast cancer: an evaluation of factors that influence patient outcomes
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/1f0e58e98d5e486282c90ca33f82886e
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Use of mTOR inhibitors in the treatment of breast cancer: an evaluation of factors that influence patient outcomes

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