Systematic Review: Comparative Effectiveness of Medications to Reduce Risk for Primary Breast Cancer

  1. Heidi D. Nelson, MD, MPH;
  2. Rongwei Fu, PhD;
  3. Jessica C. Griffin, MS;
  4. Peggy Nygren, MA;
  5. M.E. Beth Smith, DO; and
  6. Linda Humphrey, MD, MPH
  1. From Oregon Health & Science University, Veterans Affairs Medical Center, and the Women and Children's Health Research Center, Providence Health & Services, Portland, Oregon.

    Abstract

    Background: Trials demonstrate the efficacy of medications to reduce the risk for invasive breast cancer.

    Purpose: To summarize benefits and harms of tamoxifen citrate, raloxifene, and tibolone to reduce the risk for primary breast cancer.

    Data Sources: MEDLINE and Cochrane databases from inception to January 2009, Web of Science, trial registries, and manufacturer information.

    Study Selection: Predefined eligibility criteria were used to select articles. English-language reports of randomized, controlled trials (RCTs) for benefits and RCTs and observational studies for harms were included.

    Data Extraction: Two reviewers assessed study data, quality, and applicability.

    Data Synthesis: Seven placebo-controlled RCTs and 1 head-to-head trial provide results for main outcomes. Tamoxifen (risk ratio, 0.70 [95% CI, 0.59 to 0.82]; 4 trials), raloxifene (risk ratio, 0.44 [CI, 0.27 to 0.71]; 2 trials), and tibolone (risk ratio, 0.32 [CI, 0.13 to 0.80]; 1 trial) reduce risk for invasive breast cancer compared with placebo by 7 to 10/1000 women per year. Tamoxifen and raloxifene reduce estrogen receptor–positive breast cancer, but not estrogen receptor–negative breast cancer, noninvasive breast cancer, or mortality; all medications reduce fractures. Tamoxifen (risk ratio, 1.93 [CI, 1.41 to 2.64]; 4 trials) and raloxifene (risk ratio, 1.60 [CI, 1.15 to 2.23]; 2 trials) increase thromboembolic events by 4 to 7/1000 women per year; raloxifene causes fewer events than tamoxifen. Tamoxifen increases risk for endometrial cancer (risk ratio, 2.13 [CI, 1.36 to 3.32]; 3 trials) compared with placebo by 4/1000 women per year and causes cataracts compared with raloxifene. Tibolone causes strokes in older women.

    Limitations: Biases, trial heterogeneity, and few head-to-head trials limit this review. Data are lacking on doses, duration, and timing of the medications; long-term effects; and nonwhite and premenopausal women.

    Conclusion: Three medications reduce risk for primary breast cancer but increase risk for thromboembolic events (tamoxifen, raloxifene), endometrial cancer (tamoxifen), or stroke (tibolone).

    Primary Funding Source: Agency for Healthcare Research and Quality.

    Article and Author Information

    • Disclaimer: The findings and conclusions in this document are those of the authors, who are responsible for its content, and do not necessarily represent the views of the Agency for Healthcare Research and Quality. No statement in this report should be construed as an official position of the Agency or of the U.S. Department of Health and Human Services.

    • Acknowledgment: The authors thank Andrew Hamilton, MLS, MS, and Rose Campbell, MLIS, MS, for literature searches and Jennifer Nguyen for administrative assistance at the Oregon Evidence-based Practice Center at the Oregon Health & Science University. They also acknowledge the contributions of Agency for Healthcare Research and Quality Officers Shilpa Amin, MD, MBsc, and Kenneth Lin, MD, and members of the Technical Expert Panel and expert reviewers.

    • Grant Support: This manuscript is based on research conducted by the Oregon Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality, Rockville, Maryland (contract no. 290-2007-10057-1).

    • Potential Conflicts of Interest: None disclosed.

    • Requests for Single Reprints: Heidi Nelson, MD, MPH, Oregon Evidence-based Practice Center, Oregon Health & Science University, Mailcode BICC, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098; e-mail, nelsonh{at}ohsu.edu.

    • Current Author Addresses: Drs. Nelson and Humphrey, Ms. Griffin, and Ms. Nygren: Oregon Evidence-based Practice Center, Oregon Health & Science University, Mailcode BICC, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239-3098.

    • Dr. Fu: Oregon Evidence-based Practice Center, Oregon Health & Science University, Mailcode CB669, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239-3098.

    • Dr. Smith: Oregon Evidence-based Practice Center, Oregon Health & Science University, Mailcode L475, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239-3098.

    • Author Contributions: Conception and design: H.D. Nelson, J.C. Griffin, P. Nygren, L. Humphrey.

    • Analysis and interpretation of the data: H.D. Nelson, R. Fu, J.C. Griffin, P. Nygren, M.E.B. Smith, L. Humphrey.

    • Drafting of the article: H.D. Nelson, R. Fu, J.C. Griffin, P. Nygren, M.E.B. Smith, L. Humphrey.

    • Critical revision of the article for important intellectual content: H.D. Nelson, R. Fu, J.C. Griffin, P. Nygren, M.E.B. Smith, L. Humphrey.

    • Final approval of the article: H.D. Nelson, R. Fu, J.C. Griffin, P. Nygren, M.E.B. Smith, L. Humphrey.

    • Provision of study materials or patients: H.D. Nelson, M.E.B. Smith.

    • Statistical expertise: R. Fu.

    • Obtaining of funding: H.D. Nelson.

    • Administrative, technical, or logistic support: H.D. Nelson, J.C. Griffin, P. Nygren.

    • Collection and assembly of data: H.D. Nelson, R. Fu, J.C. Griffin, P. Nygren, M.E.B. Smith, L. Humphrey.

    This Article

    1. Published online before print September 14, 2009
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