Abstract A78: A randomized phase II presurgical trial of weekly tamoxifen versus raloxifene versus placebo in premenopausal women with breast cancer

Background: The presurgical model is a useful tool to test drug activity on surrogate biomarkers of breast cancer, including proliferation measured by Ki‐67. We previously demonstrated that 1 or 5 mg/per day of tamoxifen (T) given for 4 weeks before surgery reduced Ki‐67 to the same extent than the standard 20 mg/d. Given the long half‐life of T and its metabolites, a weekly dose (10 mg/w) may be worth testing. Raloxifene (R), another SERM, has been shown to reduce Ki‐67 in a preoperative setting and to be an effective breast cancer (BC) preventive agent in postmenopausal women. Methods: 125 premenopausal estrogen receptor positive BC patients were randomly assigned to either T 10mg/w or R 60 mg/d or placebo (P) for 6 weeks before surgery in a 2:2:1 ratio. The primary endpoint was tissue change of Ki67. Secondary endpoints were other tissue and circulating biomarkers. Results: The median age was 44, 46, 44 and the median BMI was 23, 22, 22 in the P, R and T group, respectively. Tissue biomarkers (Ki‐67, ER, PgR) were not significantly modulated by treatment. Only PgR was modestly down regulated by T and more by R but with not statistically significance. More evident were the effects on the circulating biomarkers. Both SERMs significantly reduced IGF‐I/BP‐3 ratio (mean change P:0; T:‐0.01; R:‐0.02; p=0.007) and cholesterol (mean change P: 13.73; T: ‐10.82; R: ‐8.96; p Conclusions: Our findings show a lack of effect of both SERMs on breast cancer cells proliferation, possibly due to insufficient doses in premenopausal women with elevated estrogen levels. In contrast, both T at very low dose and R at the standard dose were effective on circulating biomarkers. Interestingly, R was more active than T in reducing fibrinogen level, in line with its safer vascular profile. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A78.