Continuing outcomes relevant to Evista: Breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene

Background: The randomized, double-blind Multiple Outcomes of Raloxifene Evaluation (MORE) trial found that 4 years of raloxifene therapy decreased the incidence of invasive breast cancer among postmenopausal women with osteoporosis by 72% compared with placebo. We conducted the Continuing Outcomes Relevant to Evista (CORE) trial to examine the effect of 4 additional years of raloxifene therapy on the incidence of invasive breast cancer in women in MORE who agreed to continue in CORE. Methods: Women who had been randomly assigned to receive raloxifene (either 60 or 120 mg/day) in MORE were assigned to receive raloxifene (60 mg/day) in CORE (n = 3510), and women who had been assigned to receive placebo in MORE continued on placebo in CORE (n = 1703). Breast cancer incidence was analyzed by a log-rank test, and a Cox proportional hazards model was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results: During the CORE trial, the 4-year incidences of invasive breast cancer and estrogen receptor (ER)-positive invasive breast cancer were reduced by 59% (HR = 0.41; 95% CI = 0.24 to 0.71) and 66% (HR = 0.34; 95% CI = 0.18 to 0.66), respectively, in the raloxifene group compared with the placebo group. There was no difference between the two groups in incidence of ER-negative invasive breast cancer during CORE (P = .86). Over the 8 years of both trials, the incidences of invasive breast cancer and ER-positive invasive breast cancer were reduced by 66% (HR = 0.34; 95 % CI = 0.22 to 0.50) and 76% (HR = 0.24; 95% CI = 0.15 to 0.40), respectively, in the raloxifene group compared with the placebo group. During the CORE trial, the relative risk of thromboembolism in the raloxifene group compared with that in the placebo group was 2.17 (95% CI = 0.83 to 5.70). This increased risk, also observed in the MORE trial, persisted over the 8 years of both trials. Conclusions: The reduction in invasive breast cancer incidence continues beyond 4 years of raloxifene treatment in postmenopausal women with osteoporosis. No new safety concerns related to raloxifene therapy were identified during CORE. © Oxford University Press 2004, all rights reserved

Effect of once-yearly zoledronic acid on the spine and hip as measured by quantitative computed tomography: results of the HORIZON Pivotal Fracture Trial.

Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength. INTRODUCTION: To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength. METHODS: In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated. RESULTS: Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p < 0.01) and QCT (5.7%, p < 0.0001). Between-treatment differences were significant for trabecular spine (p = 0.0017) [non-parametric test], trabecular trochanter (10.7%, p < 0.0001), total hip (10.8%, p < 0.0001), and compressive strength indices at femoral neck (8.6%, p = 0.0001), and trochanter (14.1%, p < 0.0001). CONCLUSIONS: Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength