Background: We evaluated the influence of HER2 gene amplification, as determined by fluorescence in situ hybridization (FISH), on clinical outcomes (objective response rates, time to disease progression, and overall survival time) in women with metastatic breast cancer treated with trastuzumab in 3 clinical trials. Breast cancer tissue specimens were evaluated using a direct labeled, dual-probe FISH assay.
Materials and methods: Specimens with a HER2:CEP17 ratio of > or = 2:0 were considered positive for gene amplification. All specimens had previously demonstrated overexpression of HER2 protein at the 2+ or 3+ level by immunohistochemistry using the Clinical Trials Assay. Response rate, time to disease progression, and survival times were then compared between the FISH-positive and FISH-negative cohorts in each of the 3 clinical trials.
Results: Informative FISH results were obtained in 765 (96%) of the 799 patients enrolled in the 3 clinical trials. Overall, 596 (78%) were FISH-positive and 169 (22%) were FISH-negative. The proportion of FISH-positive patients was comparable in all 3 trials. Clinical benefit from trastuzumab therapy appeared to be restricted to patients with FISH-positive metastatic breast cancer. In each clinical trial, the cohort of FISH-positive patients had higher overall response rates and longer durations of survival compared with FISH-negative patients.
Conclusion: These data indicate that assessment of HER2 amplification by FISH is the preferred method to select patients for trastuzumab therapy.