Buzdar et al. stressed the effectiveness of anastro-zole (1 mg respectively 10 mg/day) as long ago as 1996. They state that the effects are similar to those of megestrol acetate, which was in trial at the same time. Anastrozole was even effective in postmenopausal women with advanced breast cancer that had progressed during tamoxifen therapy.
In 2003, Buzdar reported on new findings, comparing anastrozole (1 mg once daily) alone and in combination with tamoxifen (20 mg once daily). In summary, he states that anastrozole is quite effective: (a) in breast cancer prevention; (b) in the early stages of breast cancer as already documented; and (c) also in cases of receptor-positive cancer that has progressed since the menopause.
In the comparative studies of ATAC and tamoxi-fen (2002) an improvement in disease-free survival was demonstrable in hormone-receptor-positive, but not in hormone-receptor-negative, cases. The incidence of phase-shifted development of contralateral breast cancer was significantly lower in the group treated with anastrozole than in subjects treated with tamoxifen (P = 0.007).
In addition, tolerance of anastrozole was also superior to that of tamoxifen, anastrozole less frequently being followed by:
Endometrial carcinoma development P = 0.02
Vaginal bleeding and discharge P = 0.0001
Cerebrovascular events P = 0.0006
Venous thrombosis P = 0.0006
Tamoxifen was better tolerated than anastrozole with respect to musculoskeletal disorders and fractures (P = 0.0001 for each).
In a double blind randomized trial Domber-nowsky et al. (1998) demonstrated that the aroma-tase inhibitor letrozole has a dose-dependent effect and is more effective and better tolerated than me-gestrol acetate (Table 12) in the treatment of post-menopausal women with advanced breast cancer previously treated with antiestrogens. In a phase III randomized clinical trial Ellis et al. (2001) confirmed the results of Dombernowsky et al. (1998). They showed that in postmenopausal patients with ER- and/or PR-positive primaries the response to tamoxifen (20 mg daily: response rate 41%) was inferior to the response to letrozole (2.5 mg daily, response rate 60%).
The differences in the response rates - letrozole versus tamoxifen - were especially marked in c-erb Bl- and/or c-erb B2-positive cancer cases (RR88 versus 21%, P = 0.004).
These results led to the conclusion that c-erb Bl and c-erb B2 signaling through the ER is ligand dependent and that the growth-promoting effects of these receptor tyrosine kinases on ER-positive cancer can be inhibited by potent estrogen deprivation therapy.
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