25098819
BACKGROUND	HER2 and TOP2A gene status are assessed for diagnostic and research purposes in breast cancer with fluorescence in situ hybridization ( FISH ) .
BACKGROUND	However , FISH probes do not target only the annotated gene , while chromosome 17 ( chr17 ) is among the most unstable chromosomes in breast cancer .
BACKGROUND	Here we asked whether the status of specifically targeted genes on chr17 might help in refining prognosis of early high-risk breast cancer patients .
METHODS	Copy numbers ( CN ) for 14 genes on chr17 , 4 of which were within and 10 outside the core HER2 amplicon ( HER2 - and non-HER2-genes , respectively ) were assessed with qPCR in 485 paraffin-embedded tumor tissue samples from breast cancer patients treated with adjuvant chemotherapy in the frame of two randomized phase III trials .
RESULTS	HER2-genes CN strongly correlated to each other ( Spearman 's rho > 0.6 ) and were concordant with FISH HER2 status ( Kappa 0.6697 for ERBB2 CN ) .
RESULTS	TOP2A CN were not concordant with TOP2A FISH status ( Kappa 0.1154 ) .
RESULTS	CN hierarchical clustering revealed distinct patterns of gains , losses and complex alterations in HER2 - and non-HER2-genes associated with IHC4 breast cancer subtypes .
RESULTS	Upon multivariate analysis , non-HER2-gene gains independently predicted for shorter disease-free survival ( DFS ) and overall survival ( OS ) in patients with triple-negative cancer , as compared to luminal and HER2-positive tumors ( interaction p = 0.007 for DFS and p = 0.011 for OS ) .
RESULTS	Similarly , non-HER2-gene gains were associated with worse prognosis in patients who had undergone breast-conserving surgery as compared to modified radical mastectomy ( p = 0.004 for both DFS and OS ) .
RESULTS	Non-HER2-gene losses were unfavorable prognosticators in patients with 1-3 metastatic nodes , as compared to those with 4 or more nodes ( p = 0.017 for DFS and p = 0.001 for OS ) .
CONCLUSIONS	TOP2A FISH and qPCR may not identify the same pathology on chr17q .
CONCLUSIONS	Non-HER2 chr17 CN patterns may further predict outcome in breast cancer patients with known favorable and unfavorable prognosis .

