Results from three retrospective studies demonstrated that fluorescence in situ hybridization (FISH) testing of tumor tissue for HER2 gene amplification is an effective method of selecting women with HER2-positive metastatic breast cancer who will most likely respond to trastuzumab(Drug information on trastuzumab) (Herceptin) therapy. Data from these studies were presented at the 37th annual meeting of the American Society of Clinical Oncology (ASCO).
In the retrospective analysis of tumor tissue from women in the phase III pivotal combination trial, those who were positive for HER2 gene amplification by FISH testing survived 50% longer27 vs 18 monthswhen treated with trastuzumab plus chemotherapy, as compared to those who received chemotherapy alone.
This result contrasts with the 24% increase in survival seen when the same tumors tested positive for HER2 protein overexpression by immunohistochemistry testing.
In the phase III pivotal first-line combination trial of trastuzumab, lead author Dr. Robert Mass (a clinical scientist at Genentech) and colleagues retrospectively tested and analyzed tumor tissue from 458 of 469 patients. The goal of the trial was to determine how HER2 gene amplification, measured by FISH, compared with HER2 protein overexpression measured by immunohistochemistry in identifying patients for trastuzumab therapy. HER2 levels of 2+ and 3+ measured by immunohistochemistry were required for enrollment. (Overexpression is determined on a scale of 0 to 3+.)
Using the PathVysion FISH assay system, HER2 gene amplification was detected in 76% of the study population. Among those who tested positive by FISH, 89% were 3+ by immunohistochemistry and 31% were 2+. In the subgroup of FISH-positive patients, the addition of trastuzumab to chemotherapy resulted in an increase in the response rate to 54%, compared to 31% for those receiving chemotherapy alone. No improvement in response rates was seen in women whose tumors were negative for HER2 gene amplification by FISH (38% for trastuzumab with chemotherapy vs 37.5% for chemotherapy alone).
"These extensive retrospective analyses show us that measuring gene amplification with FISH testing may provide more accurate information about potential tumor response rates and improvement in survival with Herceptin," said Dr. Mass.