Abstract Fluorescent In Situ Hybridization (FISH) and genomic Copy Number Variation (CNV) testing may not yield identical CN status for the same gene, due to methodological differences in calling gene copies. The aim of the present study was to evaluate the clinical relevance of genomic CNV profiles on 17q (17q11.2-q12 to 17q21-q22) in the context of high-risk operable breast cancer. Methods: The CN status of NOS2, HER2, THRA, RARA and TOP2A was tested with 5’- and 3’-end-specific, exon-intron spanning qPCR CNV assays (two assays per gene). Software obtained CN values against normal DNA were evaluated from 439 informative paraffin breast cancer tissue samples with >50% tumor cells and were assessed (a) upon logarithmic transformation as continuous variables, and (b) as nominal variables with following CN categories: loss (>0-0.5 copies); no-gain or marginal accounting for DNA replication (1-4); low-gain (5-6) and high-gain (>6). For each gene, 5’- and 3’-ends were evaluated separately for gene stability and in combination for obtaining the entire gene CN status. All patients had received adjuvant anthracyclines in the frame of two phase III trials. Results: Concordance between 5’- and 3’-end CN status was observed in 94.53% of tumors for TOP2A; 91.12% for THRA; 86.79% for HER2; 69.70% for RARA; and, 53.76% for NOS2. Strong associations were observed for classic HER2 FISH status with NOS2 (p=.0007), HER2 and THRA (both p<.0001), and for classic TOP2A FISH status with HER2 (p=.0004) and THRA (p<.0001) gene CN status. Hierarchical cluster analysis based on the log-transformed CN values by using Euclidean distance and Ward's minimum variance yielded an unsupervised 7-cluster classification, whereby tumors with one or multiple low CN genes were associated with worse outcome (log-rank p=.0195 for disease free survival [DFS]). Based on this observation we used the above described CN categories and applied a deterministic profiling distinguishing tumors with no aberrations (A, n=218 [49.7%]); CN losses or complex losses/gains (B, n=29 [6.6%]); any gain in 1 gene (C, n=92 [20.9%]); and, multiple gains (D, n=100 [22.8%]). Again, patients with B-tumors had the worst outcome (p=.0123 for DFS). Upon adjustment for clinical parameters, FISH and IHC HER2 and TOP2A status, ER/PgR IHC, and breast carcinoma subtypes, B-tumors independently predicted for increased risk of relapse and death in comparison to A- and C-tumors (e.g., for DFS, B vs. A, HR: 2.3, 95%CI: 1.3-4.2, Wald-p=.0036; B vs. C, HR: 2.6, 95% CI: 1.4-5.0, Wald-p=.0031). Conclusions: Breast tumors with CN losses or complex losses/gains for the genes examined on 17q seem to carry the worst prognosis among those treated in the adjuvant setting with anthracyclines and may be worthy indentifying for different treatment selection. TOP2A FISH and CNV status are not concordant, while NOS2 and RARA seem to suffer internal CNV, which needs further validation for its biologic implications. Citation Format: Vassiliki Kotoula, Mattheos Bobos, George Kouvatseas, Christos Papadimitriou, Kyriaki Papadopoulou, Elpida Charalambous, Eleftheria Tsolaki, George Fountzilas. Genomic CNV testing on chromosome 17q genes reveals clinically relevant subtypes in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1918. doi:10.1158/1538-7445.AM2013-1918