HER2+ Breast Cancer: Biologic Relevance and Optimal Use of Diagnostic Tools
HER2+ Breast Cancer: Biologic Relevance and Optimal Use of Diagnostic Tools
Clinical laboratory testing for human epidermal growth factor receptor 2 (HER2) status in newly diagnosed breast cancer is critically important for therapeutic decision making. Unlike most pathologic testing, which serves as an adjunct to establishing a diagnosis, the results of HER2 testing stand alone in determining which patients are likely to respond to trastuzumab, a monoclonal antibody against HER2. Given the significant clinical impact of the testing results on subsequent patient management, the accuracy, precision, and reproducibility of HER2 testing are critical. At present, several preanalytic factors, including the time from tissue removal to tissue fixation, are underappreciated as important variables that have the potential to negatively impact the consistency and reliability of HER2 testing. Rigorous quality control and standardization of the testing process, from the handling of tissue samples to interpretation and reporting of results, are essential for achieving accurate and reproducible assay results.
Adenocarcinoma of the breast is a leading cause of cancer morbidity and mortality among women worldwide. A major challenge faced by clinicians treating patients with breast cancer is how to best assess patient outcomes and predict the clinical course of the disease so that the most appropriate treatment regimen can be identified.
Clinicians carefully consider several conventional prognostic factors when making treatment decisions; these include TNM staging, surgical margin status, tumor grade, lymphovascular invasion, and hormone receptor status. Many have been validated extensively in numerous studies and in many years of clinical practice. However, new prognostic markers that have been validated in robust studies are required to allow accurate individual risk assessment, particularly for patients with early-stage breast cancer.
It has become increasingly clear that the dysregulation of genes involved in controlling normal growth and development can drive cancer cell growth and survival. In some cases, this dysregulation begins with the amplification of a gene, leading to inappropriate overexpression of the protein product of the gene and disruption of normal cellular function. Protein gene products that have direct roles in driving the biology and clinical behavior of cancer cells are potential targets for the development of novel therapeutics. Research efforts have focused on the investigation and identification of new molecular factors, which can improve the predictability of risk of metastasis and the likelihood of response to therapies. The HER2 story and the development of trastuzumab (Herceptin, Genentech, South San Francisco, CA) has been one of the more remarkable developments in medical oncology, having significant implications for treatment and outcomes in patients whose tumors harbor an HER2 molecular alteration.
Clinical laboratory testing for human epidermal growth factor receptor 2 (HER2) status in newly diagnosed breast cancer is critically important for therapeutic decision making. Unlike most pathologic testing, which serves as an adjunct to establishing a diagnosis, the results of HER2 testing stand alone in determining which patients are likely to respond to trastuzumab, a monoclonal antibody against HER2. Given the significant clinical impact of the testing results on subsequent patient management, the accuracy, precision, and reproducibility of HER2 testing are critical. At present, several preanalytic factors, including the time from tissue removal to tissue fixation, are underappreciated as important variables that have the potential to negatively impact the consistency and reliability of HER2 testing. Rigorous quality control and standardization of the testing process, from the handling of tissue samples to interpretation and reporting of results, are essential for achieving accurate and reproducible assay results.
Adenocarcinoma of the breast is a leading cause of cancer morbidity and mortality among women worldwide. A major challenge faced by clinicians treating patients with breast cancer is how to best assess patient outcomes and predict the clinical course of the disease so that the most appropriate treatment regimen can be identified.
Clinicians carefully consider several conventional prognostic factors when making treatment decisions; these include TNM staging, surgical margin status, tumor grade, lymphovascular invasion, and hormone receptor status. Many have been validated extensively in numerous studies and in many years of clinical practice. However, new prognostic markers that have been validated in robust studies are required to allow accurate individual risk assessment, particularly for patients with early-stage breast cancer.
It has become increasingly clear that the dysregulation of genes involved in controlling normal growth and development can drive cancer cell growth and survival. In some cases, this dysregulation begins with the amplification of a gene, leading to inappropriate overexpression of the protein product of the gene and disruption of normal cellular function. Protein gene products that have direct roles in driving the biology and clinical behavior of cancer cells are potential targets for the development of novel therapeutics. Research efforts have focused on the investigation and identification of new molecular factors, which can improve the predictability of risk of metastasis and the likelihood of response to therapies. The HER2 story and the development of trastuzumab (Herceptin, Genentech, South San Francisco, CA) has been one of the more remarkable developments in medical oncology, having significant implications for treatment and outcomes in patients whose tumors harbor an HER2 molecular alteration.
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