K-ras mutation in the endometrium of tamoxifen-treated breast cancer patients, with a comparison of tamoxifen and toremifene.
The putative presence of a mutation in codon 12 of the K-ras gene was investigated in the endometrium of tamoxifen (TAM) and toremifene (TOR)-treated breast cancer patients. DNA was extracted from fresh cytologic samples of the endometrium in 86 TAM and 21 TOR-treated breast cancer patients. Mutations were detected by enriched PCR and an enzyme-linked mini-sequence assay (ELMA). K-ras mutation was found in 35 TAM-treated endometrial samples, and in only one TOR-treated endometrium (P<0.003). In 24 premenopausal patients, K-ras mutation was found in seven (43.8%) of 16 patients with less than 47 months of TAM treatment, while none was found in eight patients with more than 48 months of TAM treatment (P<0.03). In 62 postmenopausal-amenorrheic patients, K-ras mutation was found in three (15.8%) of 19 patients with less than 23 months of TAM treatment, while it was found in 16 (61.5%) of 26 patients with 24-47 months of TAM treatment and nine (52.9%) of 17 patients with more than 48 months of TAM treatment (P=0.002). The presence of K-ras mutation is significantly influenced by the duration of TAM treatment and menstrual status of the patients. TOR may have a lower potential genotoxicity than TAM.
Hachisuga
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T
Department of Obstetrics and Gynecology, the School of Medicine, Fukuoka University, 45-1, 7-chome, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. hachisug@fukuoka-u.ac.jp
Tsujioka
H
H
Horiuchi
S
S
Udou
T
T
Emoto
M
M
Kawarabayashi
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003062:Codon; D004717:Endometrium / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D011905:Genes, ras; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D013629:Tamoxifen / Q000627:therapeutic use*; D017312:Toremifene / Q000627:therapeutic use*; D014463:Ultrasonography
D018931:Antineoplastic Agents, Hormonal; D003062:Codon; D013629:Tamoxifen; D017312:Toremifene