Abstract P2-10-20: A tumor DNA complexity index is an independent predictor of survival in a dataset of 1950 breast cancers; a METABRIC group study

• Published in: Cancer research (Chicago, Ill.) Vol. 72; no. 24_Supplement; pp. P2 - P2-10-20
• Main Authors: Vollan, HKM, Rueda, OM, Børresen-Dale, A-L, Aparicio, S, Caldas, C
• Format: Journal Article
• Language: English
• Published: 15.12.2012
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.SABCS12-P2-10-20

Abstract Background: Cancer genomes undergo substantial alterations during carcinogenesis. Patterns of such rearrangements differ with respect to cancer subtypes and may affect crucial parts of the genome. DNA based markers would make clinical implementation more feasible as markers based on RNA expression are challenging due to the intrinsic problem of RNA stability and volatility in expression patterns. Complex genomic rearrangements in breast cancer genomes, quantified by the complex arm-wise aberration index (CAAI), have previously been shown to be of prognostic value. However this finding has not been validated in independent large-scale breast cancer cohorts or compared with other molecular predictors. Methods: A total of 1950 breast carcinomas from the METABRIC cohort with log term follow up were included in this study. Microarray based copy number and expression data from fresh frozen primary tumors were available. Cases were classified as CAAI positive if at least one complex event was present in the tumor genome. The clinical end points were breast cancer specific survival (BCSS) and overall survival (OS). Results: A total of 33 % of breast cancer cases were CAAI positive with a Cox proportional hazard ratio (HR) of 1.78 (95% CI, 1.49–2.12) for BCSS. Using multivariate Cox regression the adjusted HR for BCSS of 1.42 (95% CI, 1.12–1.80) and 1.44 (95% CI, 1.02–2.03) in estrogen receptor positive (ER+) and estrogen receptor negative breast cancers, respectively. Gene expression classifiers based on OncotypeDX and MammaPrint were not independently prognostic in the ER− subset. Significant difference in survival was both seen in patients that received systemic treatment, and in patients that did not. Conclusions: DNA based prognostic profiling is a robust method for both fresh frozen and FFPE tumor material. This study shows that complex genomic alterations of tumor DNA, measured as CAAI, is an independent predictor of survival in breast cancer, in both ER+ and ER− disease in a large scale breast cancer cohort with long term follow up. The effect seems unrelated to systemic endocrine treatment or chemotherapy. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-20.