Effect of Raloxifene on the Incidence of Invasive Breast Cancer in Postmenopausal Women with Osteoporosis Categorized by Breast Cancer Risk

Abstract

Purpose: To assess the effect of raloxifene, indicated for osteoporosis treatment and prevention, on invasive breast cancer in subgroups of postmenopausal women defined by risk factors for breast cancer. Experimental Design: Data from the 4-year Multiple Outcomes of Raloxifene Evaluation (MORE) trial (N = 7,705) and a follow-up study, the 4-year Continuing Outcomes Relevant to Evista (CORE) trial (N = 4,011), were analyzed. Prespecified subgroups were defined by age (z65 versus <65 years), age at menopause (z49 versus <49 years), body mass index (z25 versus <25 kg/m 2 ), family history of breast cancer (yes/no), serum estradiol level (5-10 versus <5, >10 versus <5 pmol/L), prior estrogen therapy (yes/no), and bone mass at MORE baseline, and 5-year predicted risk, assessed using the modified Gail model (z1.67 versus <1.67%), at CORE baseline.Time-to-first invasive breast cancer was analyzed using Cox proportional hazards models. Results: In the placebo group, older age, higher estradiol level, and a family history of breast cancer were associated with an increased breast cancer risk (P < 0.05). Raloxifene therapy was associated with a reduced breast cancer risk in both women at lower and those at higher breast cancer risk. Hazard ratio point estimates were 0.11to 0.67, corresponding to a 33% to 89% reduction in breast cancer risk with raloxifene versus placebo. The therapy by family history interaction was significant (P = 0.04). Conclusions: Raloxifene therapy was associated with a reduced risk of invasive breast cancer in postmenopausal women irrespective of the presence/absence of risk factors; its effect was greater in women with a family history of breast cancer.Identifying women most likely to benefit from breast cancer prevention strategies requires an understanding of any association between risk factors for the disease and benefits of the proposed therapeutic intervention. Women at higher risk for breast cancer are generally older and have a greater lifetime estrogen exposure, as assessed through surrogate indicators of estrogen exposure including age at menopause, body mass index (BMI), estradiol level, and use of estrogen therapy (1 -4).A heritable component to disease etiology is also well recognized and women with a first-degree relative with breast cancer are at greater risk of breast cancer (5). The Gail model (6, 7) is the most commonly used tool to estimate breast cancer risk; 5-year predicted risk is calculated based on the presence/ absence of recognized breast cancer risk factors. Using this model, women at high risk are generally defined as those with a 5-year predicted risk of invasive breast cancer of z1.67%.Tamoxifen, a selective estrogen receptor modulator, is the only agent currently approved for chemoprevention of breast cancer and is indicated in women considered at high risk for breast cancer based on their 5-year predicted risk assessed using the Gail model.Raloxifene, a selective estrogen receptor modulator indicated for osteoporosis treatment and prevention, is associated ...

Strategies for Risk Reduction

“…However, the effect was greater in women with increased risk of developing breast cancer, varying from 33% to 89% decreases in breast cancer occurrence congruent with the estimated risk. 12 This proved that the effect of raloxifene was greater in higher-risk women. Other examinations of the MORE study data have shown that the reduction of breast cancer risk seen in the use of raloxifene is dependent on the level of endogenous estrogen ( Fig.…”

Endokrine Interventionen bei Frauen mit BRCA-1/2-Mutation

“…Raloxifene increased the risk of venous thromboembolic disease (RR 3.1, 95 % CI 1.5-6.2) but not the risk of endometrial cancer (RR 9.8, 95 % CI 0.2-2.7). Lippman et al [67] analysed data from the 4-year MORE trial and a follow-up study, the 4-year Continuing Outcomes Relevant to Evista (CORE) trial. Use of raloxifene was associated with a reduced breast cancer risk in both women at lower and those at higher breast cancer risk but the effect of raloxifene was greater in women with a family history of breast cancer.…”

Raloxifene: A Selective Estrogen Receptor Modulator for Reducing the Risk of Invasive Breast Cancer in Postmenopausal Women

“…The Continuing Outcomes Relevant to Evista (CORE) trial was conducted 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 [11][12]. There were 3510 women who had been randomly assigned to receive raloxifene (either 60 or 120 mg/day) in MORE who were assigned to receive raloxifene 60 mg/day in CORE.…”

“…During the 4 years of the CORE trial, there were 61 cases of breast cancer (30 in the placebo group and 31 in the raloxifene group) that were confirmed by adjudication [11][12]. Of the 61 breast cancer cases, 52 cases (28 in the placebo group and 24 in the raloxifene group) were classified as invasive breast cancer.…”