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Current Approaches and Emerging Directions in HER2-resistant Breast Cancer

Human epidermal growth factor receptor-2 (HER2) is overexpressed in up to 30% of breast cancers; HER2 overexpression is indicative of poor prognosis. Trastuzumab, an anti-HER2 monoclonal antibody, has led to improved outcomes in patients with HER2-positive breast cancer, including improved overall s...

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Detalles Bibliográficos
Autor principal: Brufsky, Adam M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Libertas Academica 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125367/
https://www.ncbi.nlm.nih.gov/pubmed/25125981
http://dx.doi.org/10.4137/BCBCR.S9453
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author Brufsky, Adam M
author_facet Brufsky, Adam M
author_sort Brufsky, Adam M
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description Human epidermal growth factor receptor-2 (HER2) is overexpressed in up to 30% of breast cancers; HER2 overexpression is indicative of poor prognosis. Trastuzumab, an anti-HER2 monoclonal antibody, has led to improved outcomes in patients with HER2-positive breast cancer, including improved overall survival in adjuvant and first-line settings. However, a large proportion of patients with breast cancer have intrinsic resistance to HER2-targeted therapies, and nearly all become resistant to therapy after initial response. Elucidation of underlying mechanisms contributing to HER2 resistance has led to development of novel therapeutic strategies, including those targeting HER2 and downstream pathways, heat shock protein 90, telomerase, and vascular endothelial growth factor inhibitors. Numerous clinical trials are ongoing or completed, including phase 3 data for the mammalian target of rapamycin inhibitor everolimus in patients with HER2-resistant breast cancer. This review considers the molecular mechanisms associated with HER2 resistance and evaluates the evidence for use of evolving strategies in patients with HER2-resistant breast cancer.
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spelling pubmed-41253672014-08-14 Current Approaches and Emerging Directions in HER2-resistant Breast Cancer Brufsky, Adam M Breast Cancer (Auckl) Review Human epidermal growth factor receptor-2 (HER2) is overexpressed in up to 30% of breast cancers; HER2 overexpression is indicative of poor prognosis. Trastuzumab, an anti-HER2 monoclonal antibody, has led to improved outcomes in patients with HER2-positive breast cancer, including improved overall survival in adjuvant and first-line settings. However, a large proportion of patients with breast cancer have intrinsic resistance to HER2-targeted therapies, and nearly all become resistant to therapy after initial response. Elucidation of underlying mechanisms contributing to HER2 resistance has led to development of novel therapeutic strategies, including those targeting HER2 and downstream pathways, heat shock protein 90, telomerase, and vascular endothelial growth factor inhibitors. Numerous clinical trials are ongoing or completed, including phase 3 data for the mammalian target of rapamycin inhibitor everolimus in patients with HER2-resistant breast cancer. This review considers the molecular mechanisms associated with HER2 resistance and evaluates the evidence for use of evolving strategies in patients with HER2-resistant breast cancer. Libertas Academica 2014-07-29 /pmc/articles/PMC4125367/ /pubmed/25125981 http://dx.doi.org/10.4137/BCBCR.S9453 Text en © 2014 the author(s), publisher and licensee Libertas Academica Ltd. This is an open access article published under the Creative Commons CC-BY-NC 3.0 License.
spellingShingle Review
Brufsky, Adam M
Current Approaches and Emerging Directions in HER2-resistant Breast Cancer
title Current Approaches and Emerging Directions in HER2-resistant Breast Cancer
title_full Current Approaches and Emerging Directions in HER2-resistant Breast Cancer
title_fullStr Current Approaches and Emerging Directions in HER2-resistant Breast Cancer
title_full_unstemmed Current Approaches and Emerging Directions in HER2-resistant Breast Cancer
title_short Current Approaches and Emerging Directions in HER2-resistant Breast Cancer
title_sort current approaches and emerging directions in her2-resistant breast cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125367/
https://www.ncbi.nlm.nih.gov/pubmed/25125981
http://dx.doi.org/10.4137/BCBCR.S9453
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