Clinical relevance of genomic aberrations in homogeneously treated high-risk stage II/III breast cancer patients

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Abstract
Little is known about the prognostic impact of chromosome aberrations in breast cancer. The aim of our study was to determine whether genomic aberrations of prognostic relevance can be identified in the context of a clinical study using molecular cytogenetics. Paraffin‐embedded tumor samples of 44 patients with high‐risk stage II/III breast cancer were analyzed by comparative genomic hybridization. All patients received identical therapy including dose‐escalated chemotherapy followed by peripheral blood stem cell transplantation. The most frequent chromosomal aberrations were gains on chromosome arms 17q (24 cases), 1q (21 cases), 8q (17 cases), 20q (13 cases), 6p (9 cases) as well as losses on chromosome arms 13q (25 cases), 11q (20 cases), 5q (11 cases), 6q (11 cases), 9p (10 cases), 18q (10 cases), 8p (9 cases) and 16q (9 cases). In univariate analysis, the correlation with the clinical outcome revealed a higher risk for patients with tumors exhibiting 13q losses and a reduced risk for tumors exhibiting 16q losses (p = 0.020), 6q losses (p = 0.041) and estrogen‐receptor positivity (0.051). In multivariate analysis using the Cox model, only the loss of 16q exhibited borderline significance (p = 0.065). These data show that comparative genomic hybridization can be performed in the context of a clinical trial. In our subgroup of high‐risk breast cancer patients, chromosomal aberrations were valuable prognostic parameters.