Abstract 318: Hierarchical clustering analysis of array CGH data identifies clinicopathologically distinct groups of lymph-node-negative invasive breast cancer

Abstract

Abstract If high-risk group of lymph node-negative (pN0) invasive breast cancer is accurately identified by a molecular diagnosis of biopsy or surgically resected tumor specimens, it would be beneficial for choosing the most appropriate adjuvant or neoadjuvant therapies. In this study, we examined genomic copy-number alterations of the 800 cancer-related genes in 51 pN0 primary invasive breast cancers (20 relapsed and 31 non-relapsed cases) surgically resected from 51 patients at the NCCH, Tokyo, between 1990 and 1994. DNA isolated from acetone-fixed paraffin-embedded tissues using microdissection were labeled directly with fluorescence dyes and subjected to array-based comparative genomic hybridizaton (array-CGH). Although copy number differences between relapsed and non-relapsed cases were unclear, unsupervised hierarchical clustering analysis was by using these 800 cancer-related genes resulted in identification of three cluster groups with significant differences in clinical outcome. Group 1 was mostly (9 of 13) composed ER(−)/HER2(−) cases, group 2 comprised 9 ER(+)/HER2(−), 8 ER(+)/HER2(+), and 6 ER(−)/HER2(+) cases, and group 3 was mostly (12 of 15) composed of ER(+)/HER2(−) cases. By the log-rank test for overall survival (OS), group 1 showed significantly worse outcome than group 2 (p = 0.0138), but no significant difference was observed in relapse-free survival (RFS) between these groups (p = 0.17). Among 20 patients who suffered relapsed later, both OS and RFS rates of group 1 were significantly higher than those of group 2 (p = 0.0083 and 0.0018). Representative genes that amplified in group 1 were CCND2(12p13.32), CDKN1B(12p13.1), whereas those kind genes in group 2 were ERBB2(17q12), NGFR(17q21.33). This work demonstrates that hierarchical clustering of array-CGH data by using 800 cancer related genes can classify pN0 invasive breast cancers into clinically relevant groups and might pave the way to develop a new tool to estimate the risk of relapse and death in patients with pN0 breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 318. doi:10.1158/1538-7445.AM2011-318