Updated FISH Guidelines Increase Eligible HER2-Positive Breast Cancer Patients

Using 2013 guidelines from the American Society of Clinical Oncology (ASCO) and the College of American Pathologists yields more women with breast cancer who may be eligible for HER2-directed therapy (HDT), according to a new study. Using fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) helps identify women with HER2 status deemed “equivocal” who may actually benefit from HDT such as trastuzumab.

Several guidelines on HER2 testing have been published over the last 2 decades. “Depending on which guideline was used, a patient’s tumor might be classified as HER2 negative, equivocal, or positive,” wrote study authors led by Robert B. Jenkins, MD, PhD, of the Mayo Clinic in Rochester, Minnesota.

The new study analyzed HER2 testing results from 2,851 patients referred for FISH testing in 2013 and 2014 to the Mayo Clinic; IHC results were available for 1,922 (67.4%), most of which (92.8%) were performed at the referring institutions. The results were published in the Journal of Clinical Oncology.

The cohort was predominantly composed of women with IHC 2+ (84.8%) results, meaning they were deemed to have equivocal HER2 status. Using the 2013 guideline, FISH testing yielded 1,986 patients (69.7%) who were interpreted as negative or nonamplified, 460 patients (16.1%) were positive (amplified), and 405 patients (14.2%) were equivocal.

If a 2007 version of the ASCO guideline was used, substantially more patients would have qualified as negative (2,425 patients; 85.1%). Another 314 patients (11.0%) were positive, and 112 (3.9%) were equivocal. Another set of criteria published by the US Food and Drug Administration (FDA) does not include an equivocal category-using those guidelines, 86.9% of the cohort were negative and 13.1% were positive.

The 2013 guideline calls for alternative chromosome 17 probe testing as a method to resolve equivocal results. Of the 405 found to be equivocal, another 212 patients were deemed positive.

In total after final FISH interpretations, 358 additional patients were HER2-positive as compared with the 2007 guideline, and 298 additional patients were positive compared with the FDA guideline. There were 672 positive patients with the 2013 guideline, representing 23.6% of the cohort; this was significantly more than with the 2007 guideline (11%; P < .001) and with the FDA criteria (13.1%; P < .001).

“The change in criteria identifies additional women who are eligible for HDT, although these women would not have been eligible for the pivotal HDT trials,” the authors wrote. “The decision to use HDT should be taken after consideration of risks and benefits and other available HER2 test results, including IHC.”