Continuing Outcomes Relevant to Evista: Breast Cancer Incidence in Postmenopausal Osteoporotic Women in a Randomized Trial of Raloxifene
Open accessAbstract
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.
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Raloxifene is indicated for the reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis.
“Raloxifene is also indicated for the reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis [83–86].”
From Clinician’s Guide to Prevention and Treatment of Osteoporosis (2014) · cites this paper as [84]
The introduction (p. 1) says raloxifene was approved for preventing and treating postmenopausal osteoporosis, while tamoxifen was the only agent approved in the United States to reduce breast cancer incidence. Although the CORE results (p. 5) show reduced invasive breast cancer incidence with raloxifene, they do not support the claim that breast cancer risk reduction was an approved indication. (LLM, conf=0.88)
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- Authors
- Martino, S., Cauley, J. A., Barrett-Connor, E., Powles, T. J., Mershon, J., Disch, D., Secrest, R. J., Cummings, S. R., & For the CORE Investigators
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Martino, S.
- Venue
- JNCI Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-11-30
- Volume
- 96
- Issue
- 23
- Pages
- 1751-1761
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- OpenAlex
- W2166760402
- Cited by
- 684
- References
- 25
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 10 · 2023: 10 · 2022: 16 · 2021: 21 · 2020: 11 · 2019: 28 · 2018: 18 · 2017: 28 · 2016: 20 · 2015: 33 · 2014: 26 · 2013: 36 · 2012: 48
- FWCI
- 37.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Digital Access to Libraries (submittedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Eli Lilly and Company
- Pfizer
- School of Medicine, Indiana University
- Pfizer Pharmaceuticals
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- raloxifene, breast cancer incidence, postmenopausal women, osteoporosis, estrogen receptor-positive breast cancer, estrogen receptor-negative breast cancer, thromboembolism, MORE trial, selective estrogen receptor modulators, breast cancer prevention, cardiovascular events, bone mineral density, hormone replacement therapy, tamoxifen, aromatase inhibitors
- MeSH terms
- Aged, Breast Neoplasms, Double-Blind Method, Drug Administration Schedule, Female, Humans, Middle Aged, United States, Osteoporosis, Postmenopausal, Incidence, Treatment Outcome, Patient Selection, Antineoplastic Agents, Hormonal, Selective Estrogen Receptor Modulators, Estrogen Receptor Modulators, Raloxifene Hydrochloride
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