Journal of the National Cancer Institute Advance Access originally published online on June 10, 2008
JNCI Journal of the National Cancer Institute 2008 100(12):854-861; doi:10.1093/jnci/djn153
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© The Author 2008. Published by Oxford University Press.
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Reduced Incidence of Invasive Breast Cancer With Raloxifene Among Women at Increased Coronary Risk
For the Raloxifene Use for The Heart Trial Investigators
Affiliations of authors: University of California, San Francisco, and the San Francisco VA Medical Center, San Francisco, CA (DG); Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA (JAC); Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN (MJG, JS, JM); Department of Epidemiology and Health Promotion, School of Public Health, Brussels Free University (ULB), Brussels, Belgium (MK); Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY (LM); Department of Cardiac Medicine, Royal Brompton Hospital, National Heart and Lung Institute, Imperial College London, London, UK (PC); Emory University School of Medicine, Atlanta, GA (NKW); Department of Family and Preventive Medicine, and Medicine, University of California, San Diego, La Jolla, CA (EBC)
Correspondence to: Deborah Grady, MD, MPH, University of California, San Francisco, 1635 Divisadero St, Ste 600, San Francisco, CA 94115 (e-mail: deborah.grady{at}ucsf.edu).
Background: In the Raloxifene Use for The Heart trial, 10 101 postmenopausal women with coronary heart disease (CHD) or multiple CHD risk factors were randomly assigned to 60 mg/d raloxifene or to placebo and followed for a median of 5.6 years. Raloxifene, a selective estrogen receptor modulator, was found to reduce the risk of invasive breast cancer and vertebral fractures but not the risk of cardiovascular events. Here, we provide further details about breast cancer incidence by tumor characteristics, duration of treatment, and subgroup.
Methods: Reported breast cancer was adjudicated by an independent committee based on medical records and pathology reports. The primary analyses used Cox proportional hazards models with time to first breast cancer as the outcome. Subgroup effects were analyzed using similar models with terms for treatment by subgroup. All statistical tests were two-sided.
Results: As previously reported, raloxifene reduced the incidence of invasive breast cancer by 44% (hazard ratio [HR] = 0.56; 95% confidence interval [CI] = 0.38 to 0.83; absolute risk reduction = 1.2 invasive breast cancers per 1000 women treated for 1 year). The lower incidence of invasive breast cancer reflected a 55% lower incidence of invasive estrogen receptor (ER)–positive tumors (HR = 0.45; 95% CI = 0.28 to 0.72). However, raloxifene treatment did not reduce the incidence of noninvasive breast cancer or of invasive ER-negative breast cancer. The reduced incidence of invasive breast cancer was similar across subgroups, including those defined by age, body mass index, family history of breast cancer, prior use of postmenopausal hormones, and 5-year estimated risk of invasive breast cancer.
Conclusion: Raloxifene reduces risk of invasive ER-positive breast cancer regardless of a woman’s baseline breast cancer risk but does not reduce risk of noninvasive or ER-negative breast cancers. These results confirm those of the Multiple Outcomes of Raloxifene Evaluation, a previous randomized trial among women with osteoporosis.
| CONTEXT AND CAVEATS Prior knowledge Raloxifene was reported by the investigators of the RUTH (Raloxifene Use for the Heart) trial to reduce the risk of both breast cancer and vertebral fractures, but not of cardiovascular events. Study design In the RUTH trial, 10101 postmenopausal women at increased coronary risk were randomly assigned to 60 mg/d raloxifene or to a placebo, and data were analyzed after a median follow-up of 5.6 years. Here, the authors report breast cancer incidence by tumor characteristics, duration of treatment, and subgroup analysis. Contribution The 44% reduction in invasive breast cancers by raloxifene included a 55% reduction in invasive ER-positive breast cancers regardless of age, body mass, history of hormone replacement therapy, family or other breast cancer risk. Incidence of invasive ER-negative breast cancers and of noninvasive breast cancers were not affected. Implications Raloxifene appears to be effective in prevention of invasive ER-positive breast cancer but not in prevention of noninvasive cancers. Limitations Participants in the RUTH trial were selected to be at increased risk of coronary disease compared to the general population.
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Manuscript received October 17, 2007; revised March 25, 2008; accepted April 24, 2008.
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