HIGHER FREQUENCY OF GENE AMPLIFICATION IN BREAST-CANCER PATIENTS WHO RECEIVED ADJUVANT CHEMOTHERAPY

BACKGROUND. Amplification of certain genes is involved in resistance t o chemotherapy. The development of such amplification in patients by d rug treatment has not yet been established. We have assessed the appea rance of gene amplification in breast cancer patients with recurrent d isease. One group of patients had previously received adjuvant chemoth erapy (cyclophosphamide, methotrexate, 5-fluorouracil [CMF]) after sur gery. The second group had not. All of these patients had develop ed r ecurrent disease and were receiving first-line endocrine treatment (ta moxifen). METHODS. Tumor cells were obtained from the recurrent carcin oma using fine-needle biopsies. Gene copy number was determined for di hydrofolate reductase and thymidylate synthase with semiquantitative p olymerase chain reaction. Dihydrofolate reductase is involved in resis tance to methotrexate (M) and thymidylate synthetase in resistance to 5-fluoropyrimidines (F), two targets for the CMF regime. RESULTS. We f ound that amplification of the examined genes develops in higher frequ ency among patients who previously received chemotherapy (p = 0.002). CONCLUSIONS. These findings provide strong evidence for gene amplifica tion induced by drug treatment. (C) 1996 American Cancer Society.