In vitro sensitivity test of breast cancer cells to hormonal agents in a radionucleotide-incorporation assay.
Breast cancer cell lines (MCF-7, T47D, BT-20 and STT-11) and fresh cells from malignant effusions of eight breast cancer patients were examined for their in vitro sensitivity to 17 beta-estradiol (E2), tamoxifen and toremifene in a miniaturized, improved nucleic acid precursor incorporation assay (MINI assay). Seven of the eight patients received either tamoxifen or toremifene following a MINI assay and the correlation was examined between in vitro sensitivity and clinical responses to the hormonal agents. In cell lines, E2 stimulated thymidine incorporation by estrogen receptor (ER)-rich cells, MCF-7 and T47D, but not by ER-poor cells, BT-20 and STT-11. Tamoxifen induced both ER-mediated and -unmediated effects in ER-rich cells. The latter effect was also observed in ER-poor cells. Toremifene had less ER-unmediated effect in all of the cells tested than tamoxifen did. The ER-mediated effect of toremifene was weaker than that of tamoxifen in cell lines but was equipotent to tamoxifen in fresh cells. E2 affected thymidine incorporation by cells withdrawn from patients who showed a partial response to the anti-estrogens. No clear correlation was demonstrated between in vitro sensitivity to anti-estrogens of fresh cells and clinical response to these agents. The present results suggest that 1) the MINI assay is a useful system to investigate hormonal effects on breast cancer cell lines; 2) clinical responses to anti-estrogens are not predicted by in vitro response to the agents but might be predicted by the in vitro response to E2; and 3) toremifene has a smaller non-specific effect on breast cancer cells than tamoxifen and is equipotent to tamoxifen in the ER-mediated effect in vitro.
Watanabe
T
T
Department of Medicine, National Cancer Center Hospital, Tokyo.
Wu
J Z
JZ
Morikawa
K
K
Fuchigami
M
M
Kuranami
M
M
Adachi
I
I
Yamaguchi
K
K
Abe
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000032:analysis / Q000188:drug therapy / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D013936:Thymidine / Q000378:metabolism*; D017312:Toremifene
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D004958:Estradiol; D017312:Toremifene; D013936:Thymidine