Pathologic Complete Response to Trastuzumab-Based Neoadjuvant Therapy Is Related to the Level of HER-2 Amplification

L. Arnould, P. Arveux, J. Couturier, M. Gelly-Marty, C. Loustalot, F. Ettore, C. Sagan, M. Antoine, F. Penault-Llorca, B. Vasseur, P. Fumoleau, B. P. Coudert
2007 Clinical Cancer Research  
Purpose: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are used to determine human epidermal growth factor receptor-2 (HER-2) status and patient eligibility for trastuzumab therapy. Using FISH and IHC, we analyzed the relationship between pathologic complete response to trastuzumab-based neoadjuvant therapy and level of HER-2 amplification in locally advanced breast cancer. Experimental Design: Breastbiopsies from 93 HER-2^positivepatients treatedwithtrastuzumabbased
more » ... eoadjuvant therapy were centrally collected and analyzed retrospectively for HER-2 amplification using FISH and HER-2 overexpression using IHC. Tumors were classified by FISH as no, low, or high amplification. Biopsies were reassessed centrally by IHC and graded 0, 1+, 2+, or 3+. Results: HER-2 status of tumor samples as assessed by FISH and IHC correlated: 16 no amplification (11 IHC 1+ and 5 IHC 2+), 27 low amplification (26 IHC 3+ and 1 IHC 2+), and 50 high amplification (all IHC 3+). Trastuzumab-based neoadjuvant therapy achieved pathologic complete response in 35 of 93 (37.6%) tumors. Pathologic complete response rate in low-and high-amplification tumors was significantly higher than in no-amplification tumors (44% versus 6%; P < 0.004). Pathologic complete response rate in high-amplification tumors was significantly higher compared with low-amplification tumors (56% versus 22%; P < 0.005). In the subgroup of low-plus high-amplification tumors, no correlation was found between pathologic complete response rate and IHC score, treatment regimen,Tor N stage, tumor grade, or hormonal receptors. Conclusions: This is the first study to show positive correlation between level of HER-2 amplification assessed by FISH and rate of pathologic complete response to trastuzumab-based neoadjuvant treatment.
doi:10.1158/1078-0432.ccr-06-3022 pmid:17975153 fatcat:zulxowxbvrbzpm326aarxwuq5m