For the past 25 years, the
estrogen antagonist
tamoxifen has been the hormonal treatment of choice for postmenopausal patients with
hormone-sensitive metastatic and early
breast cancer (EBC). However,
tamoxifen is associated with certain tolerability and safety concerns. In addition, the hormonal options after progression are limited, and thus, alternative endocrine treatments have been developed. This review provides a synopsis of the newer alternatives in endocrine
therapy of
breast cancer: the
aromatase inhibitors (AIs) and
fulvestrant Faslodex), the
estrogen receptor antagonist that downregulates
estrogen and
progesterone receptors and has no known agonist activity. The third-generation AIs,
anastrozole and
letrozole, have been shown to be as effective or more effective than
megestrol acetate and
tamoxifen as second- and first-line
therapies for the treatment of postmenopausal patients with metastatic
breast cancer, and
exemestane has been approved for second-line use.
Fulvestrant has been shown to be as effective as
anastrozole as second-line
therapy for metastatic
breast cancer and has been approved in the U.S. for the treatment of postmenopausal women with
hormone-receptor-positive metastatic
breast cancer following progression on
antiestrogen therapy.
Anastrozole is the only AI with published clinical trial data and U.S. Food and Drug Administration approval for adjuvant
therapy of postmenopausal women with EBC. The '
Arimidex,'
Tamoxifen, Alone or in Combination (ATAC) trial, a double-blind, multicenter trial with 9,366 patients, compared
tamoxifen with
anastrozole, alone and in combination, as adjuvant endocrine treatment for postmenopausal patients with operable, invasive, EBC. The first analysis (at a median follow-up of 33.3 months) showed longer disease-free survival and, in general, better tolerability with
anastrozole than with
tamoxifen. This pattern was maintained at later analyses with a median follow-up of 47 months for efficacy and 37 months for safety and tolerability. Although longer follow-up is warranted,
anastrozole appears to be a well-documented choice of endocrine adjuvant
therapy for postmenopausal women with
hormone-responsive
breast cancer.