Clinical Notice for American Society of Clinical Oncology-College of American Pathologists guideline recommendations on ER/PgR and HER2 testing in breast cancer.

TO THE EDITOR: We wish to call your attention to a Clinical Notice (available at www.asco.org/guidelines/her2, www.asco.org/ guidelines/erpr, and http://goo.gl/96Gnl) recently released by the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) on behalf of the Human Epidermal Growth Factor Receptor 2 (HER2) and the Hormone Receptor Testing Guideline Panels. In 2007 and 2010, the two organizations issued joint guideline recommendations with the primary goal of improving the accuracy of HER2 testing and of estrogen receptor (ER) and progesterone receptor (PgR) immunohistochemical (IHC) testing in clinical practice and their utility as prognostic and predictive markers in breast cancer. Those two documents emphasize strategies to ensure optimal performance (preanalytic/analytic variables) and optimal interpretation and reporting (analytic/postanalytic variables) of established assays used in routine clinical practice. The Clinical Notice (http://goo.gl/pVdGb) reconciles the two guideline recommendations on matters of cold ischemia time, handling of specimens obtained remotely, fixation time in neutral buffered formalin, and selection of an optimal sample for testing. Assays for HER2 and for hormone receptor testing are usually performed on the same breast cancer tissue specimen, and the main purpose of this Clinical Notice is to ensure that specimens are handled in a uniform manner. In a related matter, we also wish to remind the readers of the intent of the ASCO-CAP HER2 Panel in establishing equivocal categories for these markers, which is a topic that has generated frequent discussion. In particular, the equivocal categories for HER2 were meant to trigger HER2 reflex testing using another validated assay if the first test is equivocal (IHC if an equivocal fluorescent in situ hybridization [FISH] test or FISH if an equivocal IHC test). The Panel felt this approach would provide clinicians and their patients with additional information for clinical decision making. Figure 2 of the January 2007 HER2 Guideline clearly stated that patients with a HER2/CEP17 (chromosome enumeration probe 17) FISH amplification ratio 2.0 were eligible for the trastuzumabadjuvant trials, includingthosewitharatiobetween2.0and2. 2. In a subsequent letter to Journal of Clinical Oncology in September 2007, we then revised Figure 1 of the guideline document to state that patients with a HER2 2 equivocal IHC test who had tumors with uniform intense membranestaininginmorethan10%andless than30%ofcellswerealso eligible for the trastuzumab trials. Most critical to this discussion, we then stated that “Available data from the adjuvant trials at present are insufficient to reliably exclude these patients from therapy with trastuzumab . ” The Panel did not recommend withholding anti-HER2 treatment in those patients with an equivocal HER2 test (or tests) whose results fellwithinranges thatwouldhaveallowedthemtobetreated inthe first generation of adjuvant HER2-targeted trials. Access to standardized and accurate testing for these critical prognostic and predictive biomarkers remains a critical step to ensure that patients everywhere receive the most appropriate treatment recommendations.