Arnould L et al. (2007) Pathologic complete response to trastuzumab-based neoadjuvant therapy is related to the level of HER2 amplification. Clin Cancer Res 13: 6404–6409

In patients with HER2-positive breast cancer, trastuzumab-based therapies offer substantial clinical benefits; however, little is known about the relationship between HER2 levels and pathological response. Arnould et al. recently analyzed the association between HER2 amplification levels and pathologic complete response in locally advanced breast cancer.

Using fluorescence in situ hybridization (FISH) and immunohistochemistry, HER2 amplification and overexpression were analyzed in biopsies obtained from 93 patients who had received trastuzumab in combination with chemotherapy for HER2-positive stage II/III breast cancer. Overall, 50 samples showed high HER2 amplification, while 27 and 16 samples were classified as low and no amplification, respectively. There was a significant correlation between the presence of HER2 amplification and pathologic complete response (P <0.001). Tumors with HER2 amplification had significantly higher pathologic complete response than did tumors with no HER2 amplification on FISH analysis (44% and 6%, respectively; P = 0.004). The level of HER2 amplification (high vs low) as assessed by FISH was the only variable related to complete response (P = 0.005); treatment regimen, patient age, T or N stage, hormone receptor status, tumor grade and immunohistochemical score were not significantly correlated with pathologic complete response.

This is the first study to show that levels of HER2 amplification, as assessed by FISH, have a positive correlation with the rate of pathologic complete response in patients treated with trastuzumab-based neoadjuvant therapy for stage II/III breast cancer. These findings might have important clinical implications in the treatment of patients with locally advanced HER2-positive disease.