1025 Background: Women with metastatic breast cancer (MBC) that overexpress HER2 experience improved overall survival (OS) when treated with trastuzumab. Immunohistochemistry (IHC) for HER2 protein expression and fluorescence in situ hybridization (FISH) for HER2 gene amplification are the preferred methods of determining HER2 positivity. However, not all HER2 positive patients respond equally well to trastuzumab. We describe the identification of subgroups of HER2+ patients with distinct clinical outcomes based on their quantitative levels of HER2 expression and HER2:HER2 dimerization. Methods: 75 patients with MBC drawn from six oncology clinics in Japan were assayed for HER2 expression and HER2:HER2 dimerization using FFPE specimens by the eTag assay, a proximity-based assay designed to detect and quantify protein-protein dimers. All patients had MBC, were treated with at least one chemotherapy (CT) regimen prior to receiving trastuzumab, and had FFPE specimens available for testing. 33% had at least 3 metastatic sites. 88% were selected for treatment based on IHC and 12% based on FISH. 16% were treated with trastuzumab alone and 84% with trastuzumab plus CT. Median clinical follow-up was 26 months. Cox proportional hazards and Kaplan-Meier (KM) analyses were performed. Results: The most significant variables associated with OS were the presence of brain metastases and the total number of metastases. In the overall population, correcting for the confounding influence of number of metastases, KM analyses demonstrated that patients with higher HER2 expression survived significantly longer than patients with lower HER2 expression (HR for death = 0.36, p = 0.0036). This relationship was even more significant for HER2:HER2 dimers (HR = 0.29, p = 0.0003). Conclusions: In a clinic-based population of Japanese women with MBC treated with heterogeneous prior and concomitant (with trastuzumab) CT regimens, the quantitative levels of HER2 expression and HER2:HER2 dimerization identified subsets of patients within a population of pre-selected HER2+ patients with different probabilities of long-term survival following trastuzumab treatment. No significant financial relationships to disclose.
Long-term trastuzumab treatment in HER2 positive metastatic breast cancer
