Potential of afatinib in the treatment of patients with HER2-positive breast cancer

Elena Geuna,1 Filippo Montemurro,2&ndash;4 Massimo Aglietta,1&ndash;3,5 Giorgio Valabrega1&ndash;3,51Division of Medical Oncology, Institute for Cancer Research and Treatment, Candiolo, Turin, 2Institute for Cancer Research, Candiolo, Turin, 3Foundation of Piedmont Oncology,...

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Autores principales:	Geuna E, Montemurro F, Aglietta M, Valabrega G
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/5195c2dbcebd4e67a5602716f5648cfa
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spelling	oai:doaj.org-article:5195c2dbcebd4e67a5602716f5648cfa2021-12-02T00:31:52ZPotential of afatinib in the treatment of patients with HER2-positive breast cancer1179-1314https://doaj.org/article/5195c2dbcebd4e67a5602716f5648cfa2012-08-01T00:00:00Zhttp://www.dovepress.com/potential-of-afatinib-in-the-treatment-of-patients-with-her2-positive--a10820https://doaj.org/toc/1179-1314Elena Geuna,1 Filippo Montemurro,2&ndash;4 Massimo Aglietta,1&ndash;3,5 Giorgio Valabrega1&ndash;3,51Division of Medical Oncology, Institute for Cancer Research and Treatment, Candiolo, Turin, 2Institute for Cancer Research, Candiolo, Turin, 3Foundation of Piedmont Oncology, Candiolo, Turin, 4Unit of Investigative Clinical Oncology, Candiolo, Turin, 5University Medical School of Turin, Turin, ItalyAbstract: In the absence of treatment, overexpression of the human epidermal growth factor receptor 2 (HER2) predicts a poor prognosis in breast cancer. In the last decade, monoclonal antibodies and small molecule tyrosine kinase inhibitors have significantly improved the outcome of HER2-positive breast cancer patients. However, tumor resistance and toxicities often limit the use of these therapies. For this reason, there is a compelling need for further investigation of new targeted therapies, such as afatinib, an oral irreversible pan inhibitor of the epidermal growth factor receptor (EGFR) family. This compound covalently interacts with tyrosine kinase domains, which are deeply involved in signal transduction leading to cell proliferation and protection from apoptosis. Afatinib has been studied in several Phase I clinical trials in advanced solid tumors. These trials have shown encouraging clinical activity and manageable side effects when afatinib is used either as a single agent or in combination with chemotherapy, with cutaneous adverse events and diarrhea being the most frequently observed toxicities. This review will focus on afatinib&rsquo;s clinical activity and will discuss ongoing clinical studies in HER2-positive breast cancer patients. In the scenario of the different HER2-targeted therapies, it will be important to define the best specific clinical and &ldquo;molecular&rdquo; setting for afatinib use, trying to identify predictors of resistance and response. Moreover, afatinib, which has the ability to cross the blood&ndash;brain barrier, could play a role in patients with brain metastases from breast cancer.Keywords: afatinib, brain metastasis, human epidermal growth factor receptor 2, metastatic breast cancer, monoclonal antibodies, small molecule kinase inhibitorsGeuna EMontemurro FAglietta MValabrega GDove Medical PressarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer: Targets and Therapy, Vol 2012, Iss default, Pp 131-137 (2012)
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 Geuna E Montemurro F Aglietta M Valabrega G Potential of afatinib in the treatment of patients with HER2-positive breast cancer
description	Elena Geuna,1 Filippo Montemurro,2&ndash;4 Massimo Aglietta,1&ndash;3,5 Giorgio Valabrega1&ndash;3,51Division of Medical Oncology, Institute for Cancer Research and Treatment, Candiolo, Turin, 2Institute for Cancer Research, Candiolo, Turin, 3Foundation of Piedmont Oncology, Candiolo, Turin, 4Unit of Investigative Clinical Oncology, Candiolo, Turin, 5University Medical School of Turin, Turin, ItalyAbstract: In the absence of treatment, overexpression of the human epidermal growth factor receptor 2 (HER2) predicts a poor prognosis in breast cancer. In the last decade, monoclonal antibodies and small molecule tyrosine kinase inhibitors have significantly improved the outcome of HER2-positive breast cancer patients. However, tumor resistance and toxicities often limit the use of these therapies. For this reason, there is a compelling need for further investigation of new targeted therapies, such as afatinib, an oral irreversible pan inhibitor of the epidermal growth factor receptor (EGFR) family. This compound covalently interacts with tyrosine kinase domains, which are deeply involved in signal transduction leading to cell proliferation and protection from apoptosis. Afatinib has been studied in several Phase I clinical trials in advanced solid tumors. These trials have shown encouraging clinical activity and manageable side effects when afatinib is used either as a single agent or in combination with chemotherapy, with cutaneous adverse events and diarrhea being the most frequently observed toxicities. This review will focus on afatinib&rsquo;s clinical activity and will discuss ongoing clinical studies in HER2-positive breast cancer patients. In the scenario of the different HER2-targeted therapies, it will be important to define the best specific clinical and &ldquo;molecular&rdquo; setting for afatinib use, trying to identify predictors of resistance and response. Moreover, afatinib, which has the ability to cross the blood&ndash;brain barrier, could play a role in patients with brain metastases from breast cancer.Keywords: afatinib, brain metastasis, human epidermal growth factor receptor 2, metastatic breast cancer, monoclonal antibodies, small molecule kinase inhibitors
format	article
author	Geuna E Montemurro F Aglietta M Valabrega G
author_facet	Geuna E Montemurro F Aglietta M Valabrega G
author_sort	Geuna E
title	Potential of afatinib in the treatment of patients with HER2-positive breast cancer
title_short	Potential of afatinib in the treatment of patients with HER2-positive breast cancer
title_full	Potential of afatinib in the treatment of patients with HER2-positive breast cancer
title_fullStr	Potential of afatinib in the treatment of patients with HER2-positive breast cancer
title_full_unstemmed	Potential of afatinib in the treatment of patients with HER2-positive breast cancer
title_sort	potential of afatinib in the treatment of patients with her2-positive breast cancer
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/5195c2dbcebd4e67a5602716f5648cfa
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Potential of afatinib in the treatment of patients with HER2-positive breast cancer

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