Attempts have been made to develop sublines of MCF-7 cells resistant to the growth-inhibitory actions of medroxyprogesterone acetate (MPA), dexamethazone (DEX), antioestrogens or high-dose oestradiol (Ed by prolonged exposure to high hormone concentrations. While high degrees of resistance to MPA, DEX and E, were achieved, cells remained anti-oestrogen-sensitive after prolonged treatment with 4 p~ tamoxifen (TAM) or the anti-oestrogen LY I I7018 (LY). Cells resistant to DEX were also resistant to MPA, while cells resistant to high-dose E2 remained sensitive to TAM. Cells resistant to MPA and E, appeared to be less responsive to cytotoxic drugs than wild-type cells, while resistance to DEX was associated with increased sensitivity. The responses of tumours to cytotoxic drugs may be affected by prior endocrine therapy.
Hormone treatment of patients with advanced breast cancer, though well tolerated and often effective, commonly leads to escape from growth control and must then be followed by use of a different hormone or of cytotoxic drugs. While antioestrogens and progestogens appear to act through different mechanisms (Horwitz et al., 1985) and can be used in succession with some success (Henderson, 1987), little is known about the actions of other hormones and of chemotherapeutic agents on tumours growing after escape.
The human breast cancer cell line MCF-7, which contains resistant cell populations surviving treatment with anti-oestrogens (