Women with Her2 unamplified but chromosome 17 hyperploid metatstatic breast cancer (MBC) respond to traztuzumab

Abstract

21051 Background: Guidelines for the interpretation of Her2 testing by FISH in determining therapy for Her2 positive metatstatic breast cancer generally suggest that only women with Her2 to chromosome 17 (CEP 17) amplification ratios of greater than 2.0 will benefit from traztuzumab. However, hyperploidy of chromosome 17 may lead to increased Her2 copy number despite a normal HER2/CEP 17 ratio, which may also predict response. We sought to examine hyperploid frequency in a well defined Her2 positive MBC population. We also sought to determine the time to progression (TTP) on first chemotherapy for MBC in such women, as well as their overall survival (OS) with MBC. Methods: A tissue mircoarray (TMA) with 3-fold redundancy was constructed using 0.6mm cores from primary or metatstatic paraffin embedded tumor from 124 cases which were Her2 2+ or 3+ by IHC, or amplified by FISH, on pathology report. Four micron thick TMA sections were used for HER2 IHC and HER2 FISH analysis. HER2/CEP 17 ratios of 2.0 or more was considered as amplification. If the tumor was 2+ or 3+ by IHC, greater than or equal to 3 signals for chromosome 17 were seen in a majority of cell nuclei, and the HER2/CEP17 ratio was less than 2.0, the tumor was considered hyperploid Her2 FISH negative. Results: Tissue blocks from 52 tumors delivered clearly interpretable amplification for Her2 by FISH. An additional 10 tumors (8%) were hyperploid, IHC positive (2+ or 3+), and FISH negative. Median survival (Kaplan-Meier) was 39 months (95% CI, 21–62) for women with hyperploid FISH negative tumors and 41 months (95% CI, 25–53) for women with FISH positive tumors (p=0.63, NS, Wilcoxon). Median time to progression (Kaplan-Meier) on first therapy for metastatic disease was 14 months (95% CI, 8–20) for hyperploid FISH negative tumors and 15 months (95% CI, 12–18) for women with FISH positive tumors (p=0.41, NS, Wilcoxon). Conclusions: In this analysis, women with hyperploid Her2 FISH negative IHC positive tumors had similar TTP and OS as women with Her2 FISH positive tumors. These women, although Her2 FISH negative, appeared to respond well to traztuzumab. These provocative results should be repeated on larger data sets. No significant financial relationships to disclose.