The replication error phenotype is associated with the development of distant metastases in hormonally treated patients with breast carcinoma.
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.
Department of Surgery, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. anees.chagpar@nortonhealthcare.org
Anees
A
Chagpar
Anthony
A
Magliocco
Annette
A
Kerviche
Leonard
L
Tan
Barbara
B
Walley
John F
JF
DeCoteau
D000368:Aged; D000704:Analysis of Variance; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000556:secondary; D016022:Case-Control Studies; D046508:Culture Techniques; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D018895:Microsatellite Repeats; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016019:Survival Analysis
D018931:Antineoplastic Agents, Hormonal; D004273:DNA, Neoplasm