Updated criteria outlined by ASCO may lead to an increase in the number of breast cancers that test HER2-positive.
After testing guidelines were changed in 2013 by the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP), a new study found that the amount of HER2-positive breast cancers doubled.
In a study published in the Journal of Clinical Oncology, researchers hypothesized that the updated criteria outlined in AC2013 would lead to an increase in the number of breast cancers that test HER2-positive.
“The new guidelines were established to reduce the number of equivocal cases, where HER2 status is uncertain, but we found that they did just the opposite,” said senior study author Robert Jenkins, MD, PhD. “The number of equivocal cases went up, resulting in additional testing and a much larger number of women with cancers ultimately labeled as HER2-positive.”
For the study, researchers analyzed fluorescence in-situ hybridization (FISH) results for 2851 breast cancer cases referred to the Mayo Clinic Cytogenetics Laboratory for testing between November 2013 and October 2014. Next, they compared the prevalence of HER2 FISH amplification using the 3 guidelines.
In 1998 the FDA approved the first HER2 testing guidelines for determining eligibility for HER2-directed therapy for breast cancer. In 2007, a new set of guidelines were published by ASCO/CAP (AC2007), and was later updated in 2013, changing the cut-off for equivocal and positive cases.
The results of the study showed that there was nearly double the amount (23.6%) of HER2 FISH-positive cases interpreted using AC2013, compared with the FDA guidelines (13.1%) or AC2007 (11%). Previously, Mayo researchers reported a 13% HER2-positivity rate using the FDA criteria in their clinical practice in 2000, which remained constant until the implementation of AC2013.
Since this implementation, an additional 10% to 15% of women with breast cancer were considered eligible for HER2-directed therapies, even though it is unclear if these patients would benefit from this additional treatment.
“Women who receive false positive results are not only exposed to the risks of HER2-directed therapies, but they also miss out on the treatments that could be effective against their cancer,” Jenkins said. “That is counter to the goal of personalized medicine, which, is to give the right drug to the right patient at the right time. Given the medical, financial, and psychosocial aspects of these targeted therapies, it is prudent that we prospectively identify the most optimal candidates for treatment.”
Authors noted that the recent National Surgical Adjuvant Breast and Bowel Project B-47 trial could help provide insight into whether the additional patients labeled as HER2-positive by AC2013 would actually benefit from the HER2-directed therapies.