Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple outcomes of raloxifene evaluation.

Department of Epidemiology, University of Pittsburgh, PA 15261, USA.
Breast Cancer Research and Treatment (Impact Factor: 4.2). 02/2001; 65(2):125-34.
Source: PubMed

ABSTRACT Raloxifene, a selective estrogen receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis, has shown a significant reduction in breast cancer incidence after 3 years in this placebo-controlled, randomized clinical trial in postmenopausal women with osteoporosis. This article includes results from an additional annual mammogram at 4 years and represents 3,004 additional patient-years of follow-up in this trial. Breast cancers were ascertained through annual screening mammograms and adjudicated by an independent oncology review board. A total of 7,705 women were enrolled in the 4-year trial; 2,576 received placebo, 2,557 raloxifene 60 mg/day, and 2,572 raloxifene 120 mg/day. Women were a mean of 66.5-years old at trial entry, 19 years postmenopause, and osteoporotic (low bone mineral density and/or prevalent vertebral fractures). As of 1 November 1999, 61 invasive breast cancers had been reported and were confirmed by the adjudication board, resulting in a 72% risk reduction with raloxifene (relative risk (RR) 0.28, 95% confidence interval (CI) 0.17, 0.46). These data indicate that 93 osteoporotic women would need to be treated with raloxifene for 4 years to prevent one case of invasive breast cancer. Raloxifene reduced the risk of estrogen receptor-positive invasive breast cancer by 84% (RR 0.16, 95% CI 0.09, 0.30). Raloxifene was generally safe and well-tolerated, however, thromboembolic disease occurred more frequently with raloxifene compared with placebo (p=0.003). We conclude that raloxifene continues to reduce the risk of breast cancer in women with osteoporosis after 4 years of treatment, through prevention of new cancers or suppression of subclinical tumors, or both. Additional randomized clinical trials continue to evaluate this effect in postmenopausal women with osteoporosis, at risk for cardiovascular disease, and at high risk for breast cancer.

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    • "While tamoxifen may decrease the risk of breast cancer in both BRCA1 (Narod et al., 2000) and BRCA2 (King et al., 2001) mutation carriers, use of this SERM has been associated with increased risk for endometrial carcinoma (Bergman et al., 2000; Bernstein et al., 1999; Fisher et al., 1998; Matsuyama et al., 2000; Mignotte et al., 1998; Peters-Engl et al., 1999; Pukkla et al., 2002; Ursic- Vrscaj et al., 2001). Although later generation SERMs, such as raloxifene, as yet have not been associated with the significantly increased risks for endometrial cancer that were found in patients treated with tamoxifen (Cauley et al., 2001; Martino et al., 2004; Vogel et al., 2006), the effectiveness of later SERMs for protecting against breast cancer in genetically susceptible women has not been established (Shelly et al., 2008). With these considerations, we believe that hysterectomy at the time of salpingo-oophorectomy in members of HBOC syndrome families further simplifies decisions regarding hormone replacement, chemoprophylaxis and treatment in women so highly at risk for breast, ovarian, fallopian tube and, perhaps, endometrial carcinomas with poor prognosis. "
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    Molecular oncology 05/2009; 3(2):97-137. DOI:10.1016/j.molonc.2009.02.004 · 5.94 Impact Factor
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    • "The Multiple Outcomes of Raloxifene Evaluation (MORE) trial was a multicenter, randomized, double-blind trial, in which women taking raloxifene or placebo were followed for a median of 40 months, from 1994 through 1998, at 180 clinical centers composed of community settings and medical practices in 25 countries, mainly in the US and Europe (Cummings et al 1999, 2002; Ettinger et al 1999; Cauley et al 2001; Lippman et al 2001; Grady et al 2004). Participants were a total of 7705 postmenopausal women with osteoporosis who were younger than 81 years (mean age, 66.5 years). "
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    ABSTRACT: Raloxifene hydrochloride is a selective estrogen receptor modulator (SERM) that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism, and blood clotting. Raloxifene significantly improves serum lipids and serum markers of cardiovascular disease risk, but it has no significant effect on the risk of primary coronary events. A meta-analysis of randomized, double-blind, placebo-controlled trials of raloxifene for osteoporosis showed the odds of fracture risk were 0.60 (95% confidence interval [CI] = 0.49-0.74) for raloxifene 60 mg/day compared with placebo. During 8 years of follow-up in an osteoporosis trial, the raloxifene group had a 76% reduction in the incidence of invasive ER-positive breast cancer compared with the placebo group. In the STAR trial, the incidence of invasive breast cancer was 4.30 per 1000 women-years with raloxifene and 4.41 per 1000 with tamoxifen; RR = 1.02; 95% CI, 0.82-1.28. The effect of raloxifene on invasive breast cancer was, therefore, equivalent to that of tamoxifen with more favorable rates of adverse effects including uterine malignancy and clotting events. Millions of postmenopausal women could derive net benefit from raloxifene through reduced rates of fracture and invasive breast cancer.
    Clinical Interventions in Aging 02/2008; 3(4):601-9. · 1.82 Impact Factor
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    • "The related SERM, tamoxifen, has been associated with a small but significant increase in the risk of endometrial cancer in postmenopausal women (Fisher et al. 1998). Raloxifene effectively increases bone density, decreases breast cancer incidence and does not increase endometrial cancer incidence in osteoporotic postmenopausal women (Cummings et al. 1999, Ettinger et al. 1999, Cauley et al. 2001). Based on these data, raloxifene has been evaluated against tamoxifen in the Study of Tamoxifen and Raloxifene (STAR) trial but only in postmenopausal women at elevated breast cancer risk. "
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