APPEARANCE OF AMPLIFIED THYMIDYLATE SYNTHASE OR DIHYDROFOLATE-REDUCTASE GENES IN STAGE-IV BREAST-CANCER PATIENTS RECEIVING ENDOCRINE TREATMENT

We have examined the appearance of amplification of 2 genes involved i n resistance to chemotherapy (thymidylate synthase, dihydrofolate redu ctase) in patients receiving endocrine treatment. Chronological tumor samples were obtained from breast-cancer patients with clinical stage- IV disease, using fine-needle biopsies. The presence of amplification of thymidylate synthase and dihydrofolate reductase was determined usi ng PCR in 185 fine-needle biopsies from 37 patients. None of the initi al samples of each patient showed amplification. However, in 7 of the 37 patients (19%) we detected development of gene amplification: in 2 cases of thymidylate synthase and in 5 cases of dihydrofolate reductas e. Five of the 7 patients with amplification were receiving second-lin e endocrine treatment after failing to respond to tamoxifen.