HER2 standards could be unsuitable in determining trastuzumab use

Issue: March 25, 2008

ORLANDO, Fla. – Present standards for HER2 determination may not be ideal for choosing breast cancer patients in the adjuvant setting for administration of trastuzumab, according to data presented at the 25th Annual Miami Breast Cancer Conference.

“We are not ready to prescribe trastuzumab to HER2-negative patients in the adjuvant setting yet,” said Soonmyung Paik, MD, director, Division of Pathology, National Surgical Adjuvant Breast and Bowel Project in Pittsburgh.

The current clinical definition of HER2-positivity based on expected response to trastuzumab in a metastatic setting is an immunohistochemistry score of 3+ or HER2/CEP17 ratio of >2 by fluorescence in situ hybridization, according to Paik.

Results from the National Surgical Adjuvant Breast and Bowel Project B-31 clinical trial, which examined the addition of trastuzumab to adjuvant chemotherapy, challenge whether the definition can be applied to the adjuvant setting. Data revealed that patients with HER2-negative disease displayed the same degree of benefit from trastuzumab. The findings also revealed no pattern of association between the amount of HER2 measured with currently used clinical tests and the degree of trastuzumab benefit for patients with HER2-positive disease.

According to Paik, data from trials led by the Breast International Group and the North Central Cancer Treatment Group supported the B-31 clinical trial findings. He and his colleagues also validated the central HER2 assay through whole transciptone profiling with Agilent and Affymetrix microarrays of 400 randomly selected patients from the B-31 trial. They wrote that the data clearly reported the absence of gene amplification in tumors classified as HER2-negative through central assay.

“We are just about to finish the gene refinement step. Once we identify the genes that are intersected between the initial 400 gene discovery cohort and the additional 400 gene refinement cohort from B-31, we can then build a predictive model for the benefit of trastuzumab. We are then going to have a validation study of 1,000 cases from the rest of the cases from B-31. By the end of this year, we are hoping to validate the predictor of trastuzumab [benefit],” Paik said. – by Paul Burress

Read HemOnc Today's one-on-one interview with Dr. Paik about the B-31 trial.

For more information:

Paik S. Prediction of benefit from trastuzumab. Presented at: 25th Annual Miami Breast Cancer Conference; Feb. 20-23, 2008; Orlando, Fla.