Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab
Jahnavi Gollamudi,1,* Jenny G Parvani,2,* William P Schiemann,3 Shaveta Vinayak3,4 1Department of Internal Medicine, 2Department of Biomedical Engineering, 3Case Comprehensive Cancer Center, Case Western Reserve University, 4Department of Hematology and Oncology, University Hospitals Case Medical Ce...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2016-02-01
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| Series: | Cancer Management and Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/neoadjuvant-therapy-for-early-stage-breast-cancer-the-clinical-utility-peer-reviewed-article-CMAR |
| _version_ | 1818623918309638144 |
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| author | Gollamudi J Parvani JG Schiemann WP Vinayak S |
| author_facet | Gollamudi J Parvani JG Schiemann WP Vinayak S |
| author_sort | Gollamudi J |
| collection | DOAJ |
| description | Jahnavi Gollamudi,1,* Jenny G Parvani,2,* William P Schiemann,3 Shaveta Vinayak3,4 1Department of Internal Medicine, 2Department of Biomedical Engineering, 3Case Comprehensive Cancer Center, Case Western Reserve University, 4Department of Hematology and Oncology, University Hospitals Case Medical Center, Cleveland, OH, USA *These authors contributed equally to this work Abstract: Approximately 20% of breast cancer patients harbor tumors that overexpress human epidermal growth factor receptor 2 (HER2; also known as ErbB2), a receptor tyrosine kinase that belongs to the epidermal growth factor receptor family of receptor tyrosine kinases. HER2 amplification and hyperactivation drive the growth and survival of breast cancers through the aberrant activation of proto-oncogenic signaling systems, particularly the Ras/MAP kinase and PI3K/AKT pathways. Although HER2-positive (HER2+) breast cancer was originally considered to be a highly aggressive form of the disease, the clinical landscape of HER2+ breast cancers has literally been transformed by the approval of anti-HER2 agents for adjuvant and neoadjuvant settings. Indeed, pertuzumab is a novel monoclonal antibody that functions as an anti-HER2 agent by targeting the extracellular dimerization domain of the HER2 receptor; it is also the first drug to receive an accelerated approval by the US Food and Drug Administration for use in neoadjuvant settings in early-stage HER2+ breast cancer. Here, we review the molecular and cellular factors that contribute to the pathophysiology of HER2 in breast cancer, as well as summarize the landmark preclinical and clinical findings underlying the approval and use of pertuzumab in the neoadjuvant setting. Finally, the molecular mechanisms operant in mediating resistance to anti-HER2 agents, and perhaps to pertuzumab as well, will be discussed, as will the anticipated clinical impact and future directions of pertuzumab in breast cancer patients. Keywords: breast cancer, HER2, monoclonal antibody, neoadjuvant, pertuzumab, receptor tyrosine kinase, signal transduction, trastuzumab |
| first_indexed | 2024-12-16T18:48:42Z |
| format | Article |
| id | doaj.art-357432be7e9046d38b08663bdcc58982 |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-16T18:48:42Z |
| publishDate | 2016-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-357432be7e9046d38b08663bdcc589822022-12-21T22:20:45ZengDove Medical PressCancer Management and Research1179-13222016-02-012016Issue 1213125622Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumabGollamudi JParvani JGSchiemann WPVinayak SJahnavi Gollamudi,1,* Jenny G Parvani,2,* William P Schiemann,3 Shaveta Vinayak3,4 1Department of Internal Medicine, 2Department of Biomedical Engineering, 3Case Comprehensive Cancer Center, Case Western Reserve University, 4Department of Hematology and Oncology, University Hospitals Case Medical Center, Cleveland, OH, USA *These authors contributed equally to this work Abstract: Approximately 20% of breast cancer patients harbor tumors that overexpress human epidermal growth factor receptor 2 (HER2; also known as ErbB2), a receptor tyrosine kinase that belongs to the epidermal growth factor receptor family of receptor tyrosine kinases. HER2 amplification and hyperactivation drive the growth and survival of breast cancers through the aberrant activation of proto-oncogenic signaling systems, particularly the Ras/MAP kinase and PI3K/AKT pathways. Although HER2-positive (HER2+) breast cancer was originally considered to be a highly aggressive form of the disease, the clinical landscape of HER2+ breast cancers has literally been transformed by the approval of anti-HER2 agents for adjuvant and neoadjuvant settings. Indeed, pertuzumab is a novel monoclonal antibody that functions as an anti-HER2 agent by targeting the extracellular dimerization domain of the HER2 receptor; it is also the first drug to receive an accelerated approval by the US Food and Drug Administration for use in neoadjuvant settings in early-stage HER2+ breast cancer. Here, we review the molecular and cellular factors that contribute to the pathophysiology of HER2 in breast cancer, as well as summarize the landmark preclinical and clinical findings underlying the approval and use of pertuzumab in the neoadjuvant setting. Finally, the molecular mechanisms operant in mediating resistance to anti-HER2 agents, and perhaps to pertuzumab as well, will be discussed, as will the anticipated clinical impact and future directions of pertuzumab in breast cancer patients. Keywords: breast cancer, HER2, monoclonal antibody, neoadjuvant, pertuzumab, receptor tyrosine kinase, signal transduction, trastuzumabhttps://www.dovepress.com/neoadjuvant-therapy-for-early-stage-breast-cancer-the-clinical-utility-peer-reviewed-article-CMARbreast cancerHER2monoclonal antibodyneoadjuvantpertuzumabreceptor tyrosine kinasesignal transductiontrastuzumab |
| spellingShingle | Gollamudi J Parvani JG Schiemann WP Vinayak S Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab Cancer Management and Research breast cancer HER2 monoclonal antibody neoadjuvant pertuzumab receptor tyrosine kinase signal transduction trastuzumab |
| title | Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab |
| title_full | Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab |
| title_fullStr | Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab |
| title_full_unstemmed | Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab |
| title_short | Neoadjuvant therapy for early-stage breast cancer: the clinical utility of pertuzumab |
| title_sort | neoadjuvant therapy for early stage breast cancer the clinical utility of pertuzumab |
| topic | breast cancer HER2 monoclonal antibody neoadjuvant pertuzumab receptor tyrosine kinase signal transduction trastuzumab |
| url | https://www.dovepress.com/neoadjuvant-therapy-for-early-stage-breast-cancer-the-clinical-utility-peer-reviewed-article-CMAR |
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