Appearance of amplified thymidylate synthase or dihydrofolate reductase genes in stage‐IV breast‐cancer patients receiving endocrine treatment

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Abstract
We have examined the appearance of amplification of 2 genes involved in resistance to chemotherapy (thymidylate synthase, dihydrofolate reductase) 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 using PCR in 185 fine‐needle biopsies from 37 patients. None of the initial 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 reductase. Five of the 7 patients with amplification were receiving second‐line endocrine treatment after failing to respond to tamoxifen.