Anastrozole, a selective nonsteroidal inhibitor of aromatase (theenzyme required for estrogen synthesis, Figures 40–2 and 40–5), is effective in some women whose breast tumors have become resistant to tamoxifen . Letrozole is similar. Exemestane, a steroid molecule, is an irreversible inhibitor ofaromatase. Like anastrozole and letrozole, it is approved for use in women with advanced breast cancer .
Several other aromatase inhibitors are undergoing clinical trials in patients with breast cancer. Fadrozole is an oral nonsteroidal (triazole) inhibitor of aromatase activity. These compounds appear to be as effective as tamoxifen. In addition to their use in breast cancer, aromatase inhibitors have been successfully employed as adjuncts to androgen antagonists in the treatment of precocious puberty and as primary treatment in the excessive aromatase syndrome.
Fulvestrant is a pure estrogen receptor antagonist that hasbeen somewhat more effective than those with partial agonist effects in some patients who have become resistant to tamoxifen. ICI 164,384 is a newer antagonist; it inhibits dimerization of the occupied estrogen receptor and interferes with its binding to DNA. It has also been used experimentally in breast cancer patients who have become resistant to tamoxifen. GnRH and its analogs (nafarelin, buserelin, etc) have becomeimportant in both stimulating and inhibiting ovarian function.