Response to Trastuzumab-Based Neoadjuvant Therapy Does Not Correlate with Level of HER2 Amplification While Deletion of Chromosome 17 May Predict a Poor Pathologic Response
B Quigley, G Acs, P McNab, J Shutter, H Soliman, J Kiluk, NN Esposito. H. Lee Moffitt Cancer Center, Tampa; University of South Florida, Tampa
Background: Trastuzumab-based therapy has relatively recently been used in the neoadjuvant setting for HER2+ breast cancer (BC). The reported rates of complete pathologic responses (cPR) in these patients range from 15% to 40%. The aim of this study was to identify pathologic variables predicting a cPR, and to assess the level of response with the level of HER2 amplification.
Design: The pathology and medical records of women with HER2+ BC who underwent neoadjuvant trastuzumab-based therapy were reviewed between 2008-2009. Tumors were tested prior to neoadjuvant therapy for gene amplification by FISH using the PathVysion 2-color probe set. Deletion of chromosome 17 (del17) was defined as a mean CEP17 copy number of ≤1.5 per cell. Additional pathologic data, including ER and PR status, were recorded. Estimated tumor volume reduction was based on the reported pre-neoadjuvant tumor size and the gross and microscopic estimation of residual tumor volume in the post-neoadjuvant specimen. T-test and correlation coefficient statistical analyses were performed using GraphPad software.
Results: Of the 29 cases included, 5 (17.24%) had cPRs. The mean estimated tumor volume reduction was 60% (range 0-100%), with 20.69% (6/29) showing <10% tumor volume reduction. The average HER2/CEP17 ratio was 5.40 (range 1.84-12.79). Neither the HER2 copy number nor the HER2/CEP17 ratio correlated with percent tumor volume reduction (cc = 0.106 and -0.04, respectively). There was no significant difference in the mean HER2 copy number or HER2/CEP17 ratio in the cPR group compared to the partial or non-responders. Eighty-percent (4/5) of the complete responders were ER-negative compared to 45.8% (11/24) of the remaining cases, but this difference did not reach statistical significance (p=0.33). However, tumors with del17 exhibited a poorer response than those without del17, with mean tumor reduction of 27.0% and 67.17%, respectively (p=0.0271).
Conclusions: Response to trastuzumab in the neoadjuvant setting is variable, and is likely related to complex molecular interactions rather than level of HER2 amplification, while del17 may predict a relatively poor pathologic response. These data need to be validated on larger sample sizes for confirmation of these findings.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 30, Monday Morning