Continued Breast Cancer Risk Reduction in Postmenopausal Women Treated with Raloxifene: 4-Year Results from the MORE Trial

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.

Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion

“…Raloxifene was shown to reduce breast cancer risk regardless of lifetime estrogen exposure, but the reduction was greater in those with higher lifetime exposure to estrogens [117]. Whether this benefit is due to a decrease in carcinogenesis or to lower tumor growth will be specified in the next few years.…”

Health economics of osteoporosis

“…[31] Raloxifene was not shown to significantly reduce the risk of non-vertebral fractures. However, raloxifene reduced the risk of invasive breast cancer by 72% (CI 54%-83%) [119]. In a patient subgroup (13.4% of the patients in the study) at high risk of cardiovascular events, the MORE study reported a 40% reduction in the risk of cardiovascular events (CI 5%-62%) [120].…”

“…The mean femoral neck T-score for bone mineral density (BMD) was -2.33 SD and for the lumbar spine the BMD was T-score of -2.58 SD. [31,39,119,120]. Patients were randomly assigned to receive 60 mg/d or 120 mg/d of raloxifene or matching placebo.…”

Development and evolution of therapies targeted to the estrogen receptor for the treatment and prevention of breast cancer

“…[131,132]. The anticipated result in reducing the risk of breast cancer as a beneficial side effect of treating osteoporosis propelled raloxifene into clinical trial vs. tamoxifen for the prevention of breast cancer as the primary endpoint.…”

“…A use patent for the treatment and prevention of osteoporosis was filed by Eli Lilly in 1992. Raloxifene has now been available for the treatment and prevention of osteoporosis in postmenopausal women since 1999 based on the prospective clinical trials demonstrating an approximately 40% decrease in spinal fractures [130] with the advantage over hormone replacement therapy of causing a 70% decrease in the incidence of breast cancer [131,132]. The anticipated result in reducing the risk of breast cancer as a beneficial side effect of treating osteoporosis propelled raloxifene into clinical trial vs. tamoxifen for the prevention of breast cancer as the primary endpoint.…”