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DNA Sequence Losses on Chromosomes 11p and 18q Are Associated with Clinical Outcome in Lymph Node-negative Ductal Breast Cancer¹

Department of Gynecology, University of Basel, CH-4031 Basel [A. D.], and Institute for Pathology, University of Basel, CH-4003 Basel [J. T., E. S., M. J. M., H. M.], Switzerland

Purpose: Histological and other markers alone cannot predictthe risk of disease progression in node-negative breast cancer. Several genomic aberrations have been linked to clinical outcome in breast cancer.

Experimental Design: In this study, comparative genomic hybridization was applied to screen for specific DNA copy number gains and losses in 20 pT₁/pT₂ node-negative invasive ductal carcinomas with no disease recurrence with at least 8 years of follow-up and in 20 pT₁/pT₂ node-negative tumors with distant disease recurrence.

Results: The number of genomic aberrations (copy number gains and losses) per tumor was significantly higher in tumors with disease recurrence (P < 0.05). The number of genomic aberrations was associated with histological grade (P < 0.02). Within the group of tumors with disease recurrence, the total number of genetic aberrations per tumor (P < 0.02) and the number of DNA sequence losses per tumor (P < 0.01) were significantly associated with poor survival. Of the individual loci involved, only losses at chromosomes 11p (P < 0.002) and 18q (P < 0.004) were associated with poor survival in the recurrence group. Histological grade and loss of 18q were independent prognostic variables in multivariate analysis.

Conclusions: This genome-wide analysis by comparative genomic hybridization suggests that node-negative ductal breast cancers with a high number of genomic aberrations have an increased risk of disease recurrence. The number of DNA sequence losses, particularly losses of chromosomes 11p and 18q, were associated with poor prognosis. Genes on chromosomes 11p and 18q may play a role in the progression of ductal breast carcinoma.

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