Higher frequency of gene amplification in breast cancer patients who received adjuvant chemotherapy.
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.
Lönn
U
U
Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
Lönn
S
S
Nilsson
B
B
Stenkvist
B
B
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology; D005784:Gene Amplification / Q000187:drug effects*; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000494:pharmacology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics; D016133:Polymerase Chain Reaction; D013629:Tamoxifen / Q000627:therapeutic use*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D013940:Thymidylate Synthase / Q000235:genetics
D013629:Tamoxifen; D003520:Cyclophosphamide; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase; D005472:Fluorouracil; D008727:Methotrexate