By B J A Furr
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Although oestrogen secretion was reduced with 4-acetoxy-A, gonadotrophin concentrations were found to be similar to basal control values, suggesting there may be a direct effect on gonadotrophins. Furthermore, when ovariectomized rats were treated with inhibitors, the rise in LH and FSH that usually occurs in castrates was prevented . Subsequent studies suggested that 4-OHA seems to affect gonadotrophins and aromatase with about equal potency in vivo. Since FSH is known to be involved in regulating ovarian aromatase, maintaining basal gonadotrophin concentrations would contribute to the effectiveness of 4-OHA in reducing oestrogen production.
Endocrinology 106: 19–21 27 Brodie AMH, Garrett WM, Hendrickson JR, Tsai-Morris CH (1982) Effects of 4-hydroxyandrostenedione and other compounds in the DMBA breast carcinoma model. Cancer Res 42: 3360s–3364s 28 Goss PE, Coombes RL, Powles TJ, Dowsett M, Brodie AMH (1986) Treatment of advanced postmenopausal breast cancer with aromatase inhibitor, 4-hydroxyandrostenedione-phase 2 report. Cancer Res 46: 4823–4826 29 Coombes CR, Goss P, Dowsett M, Gazet JC, Brodie A (1984) 4-Hydroxyandostenedione in treatment of postmenopausal patients with advanced breast cancer.
The effect of second-line treatment with letrozole (Let) on the growth of MCF-7Ca breast cancer xenograft tumours progressing on tamoxifen (Tam) treatment. Tumours in the mice treated with tamoxifen (100 µg/day) doubled in volume after 16 weeks of treatment. At that point, the mice were divided into three groups: for continued treatment with tamoxifen (n = 4), for second-line treatment with letrozole (10 µg/day; n = 5), and for continued treatment with letrozole (n = 5). Second-line treatment lasted for 12 weeks, and tumour volumes were measured weekly for a total of 28 weeks.