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The HER‐2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER‐2 Therapy and Personalized Medicine

Ross, Jeffrey S. ; Slodkowska, Elzbieta A. ; Symmans, W. Fraser ; Pusztai, Lajos ; Ravdin, Peter M. ; Hortobagyi, Gabriel N.

The oncologist (Dayton, Ohio), 2009-04, Vol.14 (4), p.320-368 [Periódico revisado por pares]

Durham, NC, USA: AlphaMed Press

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Título:
The HER‐2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER‐2 Therapy and Personalized Medicine
Autor: Ross, Jeffrey S. ; Slodkowska, Elzbieta A. ; Symmans, W. Fraser ; Pusztai, Lajos ; Ravdin, Peter M. ; Hortobagyi, Gabriel N.
Assuntos: Anthracyclines - administration & dosage ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Bevacizumab ; Biomarkers, Tumor - analysis ; Breast Neoplasms - chemistry ; Breast Neoplasms - drug therapy ; Breast Neoplasms - mortality ; Breast Neoplasms - pathology ; CISH ; Everolimus ; Evidence-Based Medicine ; Female ; FISH ; Gene Expression Regulation, Neoplastic - drug effects ; HER‐2 ; Humans ; IHC ; Immunohistochemistry ; In Situ Hybridization ; Lapatinib ; Neoplasm Staging ; Polymerase Chain Reaction ; Practice Guidelines as Topic ; Prognosis ; Pyrazoles - administration & dosage ; Pyrimidines - administration & dosage ; Quinazolines - administration & dosage ; Receptor, ErbB-2 - analysis ; Receptor, ErbB-2 - drug effects ; Review ; RNA, Messenger - analysis ; Sirolimus - administration & dosage ; Sirolimus - analogs & derivatives ; Survival Analysis ; Taxoids - administration & dosage ; Trastuzumab ; Treatment Outcome ; Up-Regulation - drug effects
É parte de: The oncologist (Dayton, Ohio), 2009-04, Vol.14 (4), p.320-368
Notas: Disclosures
Elzbieta A. Slodkowska
Lajos Pusztai
W. Fraser Symmans
Section editor
None.
has disclosed no financial relationships relevant to the content of this article.
Jeffrey S. Ross
Intellectual property rights
Employment/leadership position
Gabriel N. Hortobagyi
Kathleen I. Pritchard
Peter M. Ravdin
Ownership interest
The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias.
None
Adjuvant Inc.
Descrição: Learning Objectives Contrast the current strengths and limitations of the three main slide‐based techniques (IHC, FISH, and CISH) currently in clinical use for testing breast cancer tissues for HER‐2 status. Compare the efficacy of trastuzumab‐ and lapatinib‐based regimens in the adjuvant and metastatic settings as reported in published clinical trials and regulatory approval databases. Contrast the list of biomarkers that have been associated with clinical resistance to trastuzumab and lapatinib and describe their current level of validation. This article is available for continuing medical education credit at CME.TheOncologist.com. The human epidermal growth factor receptor (HER‐2) oncogene encodes a transmembrane tyrosine kinase receptor that has evolved as a major classifier of invasive breast cancer and target of therapy for the disease. The validation of the general prognostic significance of HER‐2 gene amplification and protein overexpression in the absence of anti–HER‐2 targeted therapy is discussed in a study of 107 published studies involving 39,730 patients, which produced an overall HER‐2–positive rate of 22.2% and a mean relative risk for overall survival (OS) of 2.74. The issue of HER‐2 status in primary versus metastatic breast cancer is considered along with a section on the features of metastatic HER‐2–positive disease. The major marketed slide‐based HER‐2 testing approaches, immunohistochemistry, fluorescence in situ hybridization, and chromogenic in situ hybridization, are presented and contrasted in detail against the background of the published American Society of Clinical Oncology–College of American Pathologists guidelines for HER‐2 testing. Testing issues, such as the impact of chromosome 17 polysomy and local versus central HER‐2 testing, are also discussed. Emerging novel HER‐2 testing techniques, including mRNA‐based testing by real‐time polymerase chain reaction and DNA microarray methods, HER‐2 receptor dimerization, phosphorylated HER‐2 receptors, and HER‐2 status in circulating tumor cells, are also considered. A series of biomarkers potentially associated with resistance to trastuzumab is discussed with emphasis on the phosphatase and tensin homologue deleted on chromosome ten/Akt and insulin‐like growth factor receptor pathways. The efficacy results for the more recently approved small molecule HER‐1/HER‐2 kinase inhibitor lapatinib are also presented along with a more limited review of markers of resistance for this agent. Additional topics in this section include combinations of both anti–HER‐2 targeted therapies together as well as with novel agents including bevacizumab, everolimus, and tenespimycin. A series of novel HER‐2–targeting agents is also presented, including pertuzumab, ertumaxomab, HER‐2 vaccines, and recently discovered tyrosine kinase inhibitors. Biomarkers predictive of HER‐2 targeted therapy toxicity are included, and the review concludes with a consideration of HER‐2 status in the prediction of response to non–HER‐2 targeted treatments including hormonal therapy, anthracyclines, and taxanes. In this review, the discovery and basic biology of the human epidermal growth factor receptor (HER) family of receptors are first considered. The review then considers HER‐2 targeted therapies, including trastuzumab‐based regimens in the treatment of metastatic breast cancer as well as in the adjuvant and neoadjuvant settings. The review concludes with a consideration of HER‐2 status in the prediction of response to non–HER‐2 targeted treatments.
Editor: Durham, NC, USA: AlphaMed Press
Idioma: Inglês

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The HER‐2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER‐2 Therapy and Personalized Medicine

Ross, Jeffrey S. ; Slodkowska, Elzbieta A. ; Symmans, W. Fraser ; Pusztai, Lajos ; Ravdin, Peter M. ; Hortobagyi, Gabriel N.

Durham, NC, USA: AlphaMed Press

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