Abstract P1-09-05: The RAZOR trial: a phase II prevention trial of screening plus goserilin and raloxifene versus screening alone in pre-menopausal women at increased risk of breast cancer.
Authors: J Motion, L Ashcroft, M Dowsett, J Cuzick, J Hickman, G Evans, D Eccles, R Eeles, R Greenhalgh, J Affen, S Bundred, C Boggis, J Sergeant, L Fallowfield, J Adams, A Howell
Journal: Cancer Research (2012)

Abstract Background: Observational studies indicate that oophorectomy at about age 40 reduces breast cancer risk by approximately a half in high risk women. Widespread use of risk reducing oophorectomy is unlikely to be acceptable to these women. We explored the feasibility of giving goserelin to produce reversible ovarian suppression together with raloxifene to maintain bone mineral density (BMD). Objectives: The primary study objective was adherence to treatment. Secondary objectives were uptake of randomisation, side effects/quality of life and measures of effect on bone and in serum. Methods: Recruitment was from 3 UK Family History Clinics. Consenting women at ≥ 1 in 3 lifetime risk of breast cancer were randomised to control or monthly subcutaneous goserelin 3.6 mg and raloxifene 60 mg/d orally for two years. Questionnaires (Endocrine Symptom Checklist, Trait &amp; State Anxiety, Sexual Activity &amp; Cancer Worry) measuring toxicity/quality of life were administered by nurses. Dual energy X-ray absorptiometry (DXA) BMD measurements were performed in the treatment arm annually. Lipids and collagen breakdown products were measured by standard methods. Results: 75 of 511 (14.7%) women approached agreed to randomisation (38 to treatment and 37 to control). The major reason for non-entry was fear of side effects (85%). Median age was 37 and 35 years, for the experimental (A) and control arm (B), respectively. Median follow up is 8.8 years. 20/38 in arm A and 27/37 of controls completed the 24 m study. 18/38 women in arm A withdrew (13 [34%] because of side effects) and 10/37 in arm B for various reasons including the desire for risk reducing surgery (n = 4). No significant differences were seen in the Endocrine Symptom Sub-scale, State or Trait anxiety or Cancer Worry. However, Hot flushes, night and cold sweats (together p &amp;lt;0.005), vaginal dryness (p = 0.006); loss of interest in sex, dyspareunia and reduced sexual pleasure (together p &amp;lt; 0.005) were significantly more in arm A. Despite this, 11 of 23 women in arm A when asked would have been happy to complete a potential five years of treatment. BMD declined by 3–7% and Ctx significantly increased (p &amp;lt; 0.005 each) but both returned to baseline by year 3. Lipids were unchanged. 4 women later developed breast cancer in arm B and 2 in arm A. Conclusions: Uptake and adherence to treatment was relatively low in this group of women at high risk. The major reason for low uptake was fear of side effects and these were the major reason for drop out from treatment. Raloxifene did not maintain BMD. This approach to breast cancer prevention induced significant symptoms and bone loss, thus methods to ameliorate these need to be developed if ovarian suppression is to play a role in breast cancer prevention. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-09-05.