HER2 Testing in Breast Cancer: ASCO/CAP Updated Guidelines

The 2013 updated American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines provide oncologists and pathologists with a number of key recommendations for testing the status of human epidermal growth factor receptor 2 (HER2) in breast cancer [J Clin Oncol. 2013;31:3897-4009].

Among the key recommendations for oncologists is that HER2 status should be determined in all patients with invasive breast cancer based on ≥1 HER2 test results. For pathologists, a key recommendation is to ensure that at least 1 sample from all patients with early-stage or metastatic breast cancer is tested for HER2 protein expression by immunohistochemistry (IHC) assay or HER2 gene expression by in situ hybridization (ISH) assay.

"A key feature of the 2013 ASCO/CAP HER2 testing guideline updates is our ability to better discriminate between HER2-positive and negative results, thereby reducing the frequency of equivocal or inconclusive test results,” said cochair of the guideline panel, Antonio C. Wolff, MD, Professor of Oncology, Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, Maryland, during an interview with First Report Managed Care. “This is a direct result of greater standardization of tissue handling, improved laboratory performance of HER2 testing, and more careful reporting of test results in the United States and elsewhere observed in clinical practice following the publication of the first guidelines in 2007. Consequently, we were able to expand our focus beyond earlier concerns about false-positive test results.” See Table (Below) for key recommendations for HER2 testing in breast cancer.

The guidelines were developed jointly by representatives of ASCO and CAP and included coauthors of the 2007 guidelines. The Update Committee was formed in 2012 to conduct a systematic review of peer-reviewed literature published since 2006 to identify criteria and areas that require clarification to improve the accuracy of HER2 testing by IHC or ISH. Studies included in the systematic review included randomized controlled trials, cohort designs, case series, evaluation studies, and comparative studies. Case reports were excluded. Both organizations reviewed and approved the guidelines.

The Update Committee used the information obtained from the systematic review to develop new algorithms for HER2 testing for both pathologists and oncologists. In addition, the information was used to specify the requirements and exclusions for testing, as well as to facilitate quality assurance monitoring to reduce the variability of HER2 testing and to ensure more analytic consistency between laboratories.

According to Dr. Wolff, the new guidelines also allowed the committee to be more specific about less common clinical scenarios because of the greater clinical experience and new data available since the 2007 guidelines. He emphasized that the ultimate goal of the guidelines is to provide clinicians and patients the best information to allow individualized clinical decision-making.

The guidelines also include key points for clinicians to discuss with patients regarding HER2 status. Among them are the following:

• The need to explain the importance of determining the biological characteristics of breast cancer

• The importance of HER2 testing

• The type of tissue used for HER2 testing

• The types of tests used to determine HER2 status

• How HER2 test results are interpreted

• The importance of retesting HER2 status in new, metastatic tumors

• Educating that HER2 testing guidelines exist

“These guidelines are a living document that will continue to evolve over time, and we want oncologists and pathologists to use it as a tool to foster improved communication and education of all healthcare providers and health systems involved in the care of breast cancer patients,” said Dr. Wolff.