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  • Title: The replication error phenotype is associated with the development of distant metastases in hormonally treated patients with breast carcinoma.
    Author: Chagpar A, Magliocco A, Kerviche A, Tan L, Walley B, DeCoteau JF.
    Journal: Cancer; 2004 Mar 01; 100(5):913-9. PubMed ID: 14983485.
    Abstract:
    BACKGROUND: The positive replication error (RER+) phenotype defines a distinct subgroup of tumors with specific clinical, pathologic, and molecular features that have been documented well in hereditary nonpolyposis colon carcinoma (HNPCC). More recently, this phenotype also has been described in breast carcinoma. METHODS: To determine the effect of RER phenotype on prognosis in patients with breast carcinoma, the authors examined matched archival tumor and normal tissue from 100 women with Stage I and Stage II breast carcinoma, all of whom were treated with hormonal therapy. Patients had been followed for a minimum of 5 years or until death. Seven microsatellite loci were examined, including hMLH1 (3p22, D3S1611), hMSH2 (2p16, D2S123), NM23-H1 (17q21), TP53-Dint (17p13), TP53-Penta (17p13), APC (5q21, D5S346), and HPC1 (1q24, D1S2883). The RER+ phenotype was defined as the presence of allelic shifts at three of the seven loci examined. RESULTS: Twenty-five percent of patients were classified with the RER+ phenotype based on these criteria. The two groups, women with positive RER status and women with negative RER status, were comparable in terms of other factors that may influence prognosis: age, tumor size, lymph node status, disease stage, and estrogen receptor status. The development of distant metastases to the lung, liver, or brain was correlated significantly with the positive RER phenotype, with a relative risk of 2.625 (95% confidence interval, 1.059-6.057). CONCLUSIONS: The presence of high-frequency RER+ may predict for the development of distant metastatic disease in patients with early-stage breast carcinoma who are treated with hormonal therapy.
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