Correlation of Allelic Loss with Poor Postoperative Survival in Breast Cancer

BACKGROUND: Allelic losses of tumor suppressor genes or the chromosomal regions harboring them in the DNA of tumor cells may become useful postoperative prognostic indicators. METHODS: To examine whether specific allelic losses correlate with postoperative survival in a five-year prospective follow-up, we tested tumors from a cohort of 504 breast cancer patients for allelic loss of 18 microsatellite markers representing either known tumor suppressor genes or regions where genetic alterations are frequent in breast tumors. RESULTS: Patients with allelic loss at 1p34, 3p25, 8p22, 13q12, 17p13.3, or 17q21.1 had a significantly higher risks of postoperative mortality compared withthose whose tumors retained both alleles at those loci (at 1p34, the 5-year mortality rate was 23% among patients with loss vs 10% with retention, p 0.0100; at 3p25, 22% vs 9%, p =0.0014; at 8p22, 24% vs 7%, p =0.0177; at 13q12, 19%vs 8%, p=0.0093; at 17p13.3, 19% vs 9%, p=0.0078; and at 17q21.1, 17% vs 10%, p =0.0475). CONCLUSION: Allelic losses at these loci can serve as negative prognostic indicators to guide post-operative management, especially in the selection of thosewho will benefit from intensive adjuvant therapies.