Reference Laboratory Identifies Change in Pattern of Breast Cancer HER2 Fluorescence in Situ Hybridization Results
The most recent (2013) ASCO/College of American Pathologists (AC) guidelines for HER2 testing resulted in different rates of HER2 positivity compared with the use of the U.S. Food and Drug Administration (FDA) or 2007 AC guidelines, according to a study reported in the Journal of Clinical Oncology by Shah et al.
Study Details
The study involved 2,851 samples sent to the Mayo Clinic cytogenetics laboratory for fluorescence in situ hybridization (FISH) testing between November 2013 and October 2014. Of them, immunohistochemistry (IHC) results were available for 1,922 (67%; 137 from the Mayo Clinic).
HER2 FISH-Positive Rates
IHC results were 0 for 2.4%, 1+ for 7.9%, 2+ for 84.8%, and 3+ for 2.5% of samples. Among IHC 2+ patients, HER2 FISH positivity was 11.8% with the FDA guidelines, 9.4% with the 2007 AC guidelines, and 24.1% with the 2013 AC guidelines. Overall, 11.8% of samples were positive with a FISH ratio ≥ 2.0; 1.3%, with a FISH ratio ≥ 2.0 despite a HER2 signal ≥ 4.0; and 3.0%, with a HER2 signal ≥ 6.0 despite a FISH ratio < 2.0.
Among 405 patients (14.2%) initially considered FISH-equivocal on the 2013 AC guidelines (ratio < 2.0 with a HER2 signal ≥ 4.0 and < 6.0), use of an alternative FISH probe indicated that 212 (7.4% overall) were FISH-positive, 36 (1.3% overall) were FISH-negative, and 157 (5.5% overall) were FISH-equivocal. Final HER2 positivity rates were 23.6% on the 2013 AC guidelines, compared with 13.1% on the FDA guidelines and 11% on the 2007 AC guidelines (P < .001 for both comparisons).
The investigators concluded: “In a reference laboratory cohort that was highly enriched for IHC 2+ patient samples, AC2013 guidelines led to a larger number of FISH-equivocal patients. Approximately one half of these FISH-equivocal patients (7.4% overall) became HER2-positive upon alternative FISH probe testing. However, these patients would not have participated in the pivotal [HER2-directed therapy] trials. Clinical utility data on [HER2-directed therapy] benefit in these patients and other special subsets are needed.”
Robert B. Jenkins, MD, PhD, of the Mayo Clinic, Rochester, Minnesota, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
