Is It Too Soon to Start Reporting Her2 Genetic Heterogeneity? (Letters to the Editor) (Letter to the Editor‪)‬

To the Editor.--Guidelines for assessing and reporting HER2 results in invasive breast cancer were recently updated by the College of American Pathologists (CAP) to address the issue of intratumoral heterogeneity. A panel of pathologists met during a group meeting held by conference call in 2008 to develop the updated guidelines, and the final recommendations were approved by the entire group and published in April of 2009 in the ARCHIVES. (1) The guidelines expand those published in 2007 by the CAP and the American Society of Clinical Oncology (ASCO). (2) The purpose of the revision was to improve the accuracy and consistency of HER2 testing in breast cancer. We are concerned, however, that the reporting of HER2 genetic heterogeneity (GH) may produce greater inconsistency of HER2 testing and lead to confusion about a patient's clinical HER2 status. The CAP panel lowered the threshold for HER2 positivity by defining HER2 amplification as a ratio of HER2/CEP17 higher than 2.2 in more than 50% of the invasive tumor cells. In addition, they defined HER2 GH as a ratio of HER2 /CEP17 higher than 2.2 in more than 5% but less than 50% of the invasive tumor cells. By this definition, if 60 cells are examined and 3 or more cells have a ratio higher than 2.2, the tumor fulfills criteria for HER2 GH. If HER2 GH is identified, the panel recommended that the pathology report include the statement that HER2 GH is present. Although one of the panel's goals was to improve reporting consistency, it is not clear that this modification will improve consistency of HER2 testing. It seems more likely that it will create, in addition to the equivocal category included in the current CAP/ASCO guidelines, another gray zone of tumors that are equivocal for HER2 GH.