Higher frequency of gene amplification in breast cancer patients who received adjuvant chemotherapy

Abstract

BACKGROUND. Amplification of certain genes is involved in resistance to chemotherapy. The development of such amplification in patients by drug treatment has not yet been established. We have assessed the appearance of gene amplification in breast cancer patients with recurrent disease. One group of patients had previously received adjuvant chemotherapy (cyclophosphamide, methotrexate, 5-fluorouracil [CMF]) after surgery. The second group had not. All of these patients had developed recurrent disease and were receiving first-line endocrine treatment (tamoxifen). METHODS. Tumor cells were obtained from the recurrent carcinoma using fine-needle biopsies. Gene copy number was determined for dihydrofolate reductase and thymidylate synthase with semiquantitative polymerase chain reaction. Dihydrofolate reductase is involved in resistance to methotrexate (M) and thymidylate synthetase in resistance to 5-fluoropyrimidines (F), two targets for the CMF regime. RESULTS. We found that amplification of the examined genes develops in higher frequency among patients who previously received chemotherapy (p = 0.002). CONCLUSIONS. These findings provide strong evidence for gene amplification induced by drug treatment.