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Allelic Loss at 1p34–36 Predicts Poor Prognosis in Node-negative Breast Cancer¹

Department of Gerontology, Nippon Medical School, Kawasaki 211-8533 [Y. U., M. E.]; Department of Surgery and Pathology, Cancer Institute, Toshima-ku 170-8455 [Y. U., M. Y., F. K., F. A., G. S.]; Department of Surgery, Daini Hospital, Tokyo Women’s Medical University, Tokyo 116-8567 [Y. U., S. H., T. K.]; and Laboratory of Molecular Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 [Y. N.], Japan

Allelic losses of specific chromosomal regions in the DNA of tumor cells, which imply loss of tumor suppressor genes normally resident at those loci, may become useful postoperative prognostic indicators for breast cancers that have not yet metastasized to lymph nodes. To examine whether specific allelic losses might correlate with postoperative disease-free survival, we tested tumors from a cohort of 228 node-negative breast cancer patients for allelic losses at 18 microsatellite loci chosen to represent either a known tumor suppressor gene or a region where genetic alterations are frequent in breast tumors. We followed the patients clinically for 5 years or until death (if patient death occurred before completion of 5 years of follow-up). Patients whose tumors had lost an allele at 1p34–36 bore significantly higher risks of postoperative recurrence than those whose tumors retained both alleles of the markers in that region [the 5-year recurrence rate was 15% among patients with losses versus 2% among patients with retention (P = 0.001)]. Multivariate analysis demonstrated that allelic loss at 1p34–36 was an independent postoperative predictor of shorter disease-free survival (hazard ratio, 5.8; P = 0.0117). Thus, allelic losses at 1p34–36 in a tumor might have a potential to serve as a negative prognostic indicator to guide postoperative management of breast cancer patients, especially in the selection of high-risk women who will benefit from adjuvant chemotherapy and endocrine therapy.

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