New HER2-testing guidelines result in more women eligible for HER2-directed treatment

New guidelines for immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) pathology testing categorize more breast cancers as “equivocal” regarding HER2 positivity and ultimately lead to identifying more of them as HER2 positive, investigators reported online in Journal of Clinical Oncology.

The American Society of Clinical Oncology and the College of American Pathologists released updated IHC and FISH guidelines in 2013, after the Food and Drug Administration approved the initial set of such guidelines in 1998 and ASCO/CAP issued their first such guidelines in 2007. “The intent of the 2013 guidelines was to decrease the number of equivocal [cancers],” said Mithun Vinod Shah, MD, PhD, of the Mayo Clinic, Rochester Minn., and his associates.

To assess the impact of implementing the new guidelines, the investigators analyzed 2,851 breast cancer samples sent to their cytogenetics laboratory by 139 medical centers for HER2 testing during a 1-year period. They compared the three sets of testing criteria – the FDA, the 2007, and the 2013 guidelines.

According to the 2013 guidelines, 69.7% of the tumors were classified as HER2 negative, 16.1% as HER2 positive, and 14.2% as equivocal. In contrast, the 2007 guidelines classified 85.1% as negative, 11.0% as positive, and 3.9% as equivocal, while the FDA guidelines classified 13.1% as positive and 86.9% as negative (there is no “equivocal” category in the FDA guidelines). Thus, “the final FISH interpretations indicate that by using 2013 guidelines, 358 additional patients were interpreted as positive, compared with the 2007 guidelines and that 298 additional patients were considered positive, compared with the FDA criteria,” Dr. Shah and his associates said.

The 2013 guidelines recommend additional chromosome 17 probe testing (among other strategies) to resolve equivocal results, so the investigators did so with the 405 samples classified as equivocal by the 2013 criteria. This resulted in 52.3% of the 405 equivocal tumors being reclassified as HER2 positive, 8.9% being reclassified as HER2 negative, and 38.8% remaining equivocal. Thus, HER2 positivity in the overall cohort rose significantly to 23.6% using the newest guidelines.

These findings demonstrate that using the 2013 guidelines for IHC and FISH pathology testing identifies more women who are eligible for HER2-directed therapy, the investigators said (J Clin Oncol. 2016 Jul 25. doi: 10.1200/JCO.2015.61.8983).

New guidelines for immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) pathology testing categorize more breast cancers as “equivocal” regarding HER2 positivity and ultimately lead to identifying more of them as HER2 positive, investigators reported online in Journal of Clinical Oncology.

The American Society of Clinical Oncology and the College of American Pathologists released updated IHC and FISH guidelines in 2013, after the Food and Drug Administration approved the initial set of such guidelines in 1998 and ASCO/CAP issued their first such guidelines in 2007. “The intent of the 2013 guidelines was to decrease the number of equivocal [cancers],” said Mithun Vinod Shah, MD, PhD, of the Mayo Clinic, Rochester Minn., and his associates.

To assess the impact of implementing the new guidelines, the investigators analyzed 2,851 breast cancer samples sent to their cytogenetics laboratory by 139 medical centers for HER2 testing during a 1-year period. They compared the three sets of testing criteria – the FDA, the 2007, and the 2013 guidelines.

According to the 2013 guidelines, 69.7% of the tumors were classified as HER2 negative, 16.1% as HER2 positive, and 14.2% as equivocal. In contrast, the 2007 guidelines classified 85.1% as negative, 11.0% as positive, and 3.9% as equivocal, while the FDA guidelines classified 13.1% as positive and 86.9% as negative (there is no “equivocal” category in the FDA guidelines). Thus, “the final FISH interpretations indicate that by using 2013 guidelines, 358 additional patients were interpreted as positive, compared with the 2007 guidelines and that 298 additional patients were considered positive, compared with the FDA criteria,” Dr. Shah and his associates said.

The 2013 guidelines recommend additional chromosome 17 probe testing (among other strategies) to resolve equivocal results, so the investigators did so with the 405 samples classified as equivocal by the 2013 criteria. This resulted in 52.3% of the 405 equivocal tumors being reclassified as HER2 positive, 8.9% being reclassified as HER2 negative, and 38.8% remaining equivocal. Thus, HER2 positivity in the overall cohort rose significantly to 23.6% using the newest guidelines.

These findings demonstrate that using the 2013 guidelines for IHC and FISH pathology testing identifies more women who are eligible for HER2-directed therapy, the investigators said (J Clin Oncol. 2016 Jul 25. doi: 10.1200/JCO.2015.61.8983).

New guidelines for immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) pathology testing categorize more breast cancers as “equivocal” regarding HER2 positivity and ultimately lead to identifying more of them as HER2 positive, investigators reported online in Journal of Clinical Oncology.

The American Society of Clinical Oncology and the College of American Pathologists released updated IHC and FISH guidelines in 2013, after the Food and Drug Administration approved the initial set of such guidelines in 1998 and ASCO/CAP issued their first such guidelines in 2007. “The intent of the 2013 guidelines was to decrease the number of equivocal [cancers],” said Mithun Vinod Shah, MD, PhD, of the Mayo Clinic, Rochester Minn., and his associates.

To assess the impact of implementing the new guidelines, the investigators analyzed 2,851 breast cancer samples sent to their cytogenetics laboratory by 139 medical centers for HER2 testing during a 1-year period. They compared the three sets of testing criteria – the FDA, the 2007, and the 2013 guidelines.

According to the 2013 guidelines, 69.7% of the tumors were classified as HER2 negative, 16.1% as HER2 positive, and 14.2% as equivocal. In contrast, the 2007 guidelines classified 85.1% as negative, 11.0% as positive, and 3.9% as equivocal, while the FDA guidelines classified 13.1% as positive and 86.9% as negative (there is no “equivocal” category in the FDA guidelines). Thus, “the final FISH interpretations indicate that by using 2013 guidelines, 358 additional patients were interpreted as positive, compared with the 2007 guidelines and that 298 additional patients were considered positive, compared with the FDA criteria,” Dr. Shah and his associates said.

The 2013 guidelines recommend additional chromosome 17 probe testing (among other strategies) to resolve equivocal results, so the investigators did so with the 405 samples classified as equivocal by the 2013 criteria. This resulted in 52.3% of the 405 equivocal tumors being reclassified as HER2 positive, 8.9% being reclassified as HER2 negative, and 38.8% remaining equivocal. Thus, HER2 positivity in the overall cohort rose significantly to 23.6% using the newest guidelines.

These findings demonstrate that using the 2013 guidelines for IHC and FISH pathology testing identifies more women who are eligible for HER2-directed therapy, the investigators said (J Clin Oncol. 2016 Jul 25. doi: 10.1200/JCO.2015.61.8983).