RAZOR: a phase II open randomized trial of screening plus goserelin and raloxifene versus screening alone in pre-menopausal women at increased risk of breast cancer
Cancer Epidemiology, Biomarkers and Prevention
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Background. Ovarian suppression in premenopausal women is known to reduce breast cancer risk. This study aimed to assess uptake and compliance with ovarian suppression using the LHRH analogue, goserelin, with add-back raloxifene, as a potential regimen for breast cancer prevention. Methods. Women at ≥30% lifetime risk breast cancer were approached and randomized to mammographic screening alone(C-Control) or screening in addition to monthly subcutaneous injections of 3.6mg goserelin and continuous 60mg raloxifene daily orally(T-Treated) for two-years. The primary endpoint was therapy adherence. Secondary end points were toxicity/quality of life, change in bone density and mammographic density. Results. 75/950 (7.9%) women approached agreed to randomization. In the T-arm, 20/38 (52%) of women completed the two-year period of study compared with the C-arm (27/37, 73.0%). Drop-outs were related to toxicity but also the wish to have established risk-reducing procedures and proven chemoprevention. As relatively few women completed the study, data are limited, but those in the T-arm reported significant increases in toxicity and sexual problems, no change in anxiety and less cancer worry. Lumbar spine bone density declined by 7.0 % and visually assessed mammographic density by 4.7% over the two-year treatment period. Conclusion Uptake is somewhat lower than comparable studies with tamoxifen for prevention with higher drop-out rates. Raloxifene may preserve bone density but reduction in mammographic density reversed after treatment was completed. Impact. This study indicates that breast cancer risk reduction may be possible using LHRH agonists, but reducing toxicity and preventing bone changes would make this a more attractive option.