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 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.
Lönn
U
U
Karolinska Hospital, Stockholm, Sweden.
Lönn
S
S
Stenkvist
B
B
D000616:Aminoglutethimide / Q000627:therapeutic use; D001483:Base Sequence; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004351:Drug Resistance; D005260:Female; D005784:Gene Amplification; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011374:Progesterone / Q000627:therapeutic use; D013629:Tamoxifen / Q000627:therapeutic use; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D013940:Thymidylate Synthase / Q000235:genetics*; D013997:Time Factors
D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides; D013629:Tamoxifen; D000616:Aminoglutethimide; D011374:Progesterone; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase