Meta-analysis of Vascular and Neoplastic Events Associated with Tamoxifen


  • R. Scott Braithwaite MD,

    Corresponding authorSearch for more papers by this author
  • Rowan T. Chlebowski MD, PhD,

  • Joseph Lau MD,

  • Suzanne George MD,

  • Rachel Hess MD,

  • Nananda F. Col MD, MPP, MPH, FACP

  • Received from the Section of Clinical Systems Modeling and Division of General Internal Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pa (RSB, RH); Harbor-UCLA Research and Education Institute, Torrance, Calif (RTC); Tufts-New England Medical Center, Boston, Mass (JL); Dana Farber Cancer Center, Harvard Medical School, Boston, Mass (SG); and the Decision Systems Group and Division of General Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass (NFC).

  • Presented at the 22nd National Meeting of the Society for Medical Decision Making and awarded the Lee B. Lusted Prize.

Address correspondence and requests for reprints to: Dr. Braithwaite, Section of Clinical Systems Modeling, Division of General Internal Medicine, Department of Medicine, University of Pittsburgh, 933 W-MUH, 200 Lothrop Street, Pittsburgh, PA 15213 (e-mail:


OBJECTIVE:  Tamoxifen reduces the risk of developing breast cancer but also affects the risks of certain vascular and neoplastic events. Our purpose was to estimate the effects of tamoxifen on potentially life-threatening vascular and neoplastic outcomes.

DESIGN:  Random effects meta-analysis of published randomized controlled trials.

PATIENTS:  Participants in all trials in which a treatment arm that included tamoxifen was compared to a similar control arm. Breast cancer risk reduction and treatment trials were included.

INTERVENTIONS:  Tamoxifen at variable dose and duration.

MEASUREMENTS AND MAIN RESULTS:  Thirty-two trials (52,929 patients) reported one or more outcomes of interest. Tamoxifen was associated with significantly increased risks of endometrial cancer (relative risk [RR] 2.70; 95% CI, 1.94 to 3.75), gastrointestinal cancers (RR 1.31; 95% CI, 1.01 to 1.69), strokes (RR 1.49; 95% CI, 1.16 to 1.90), and pulmonary emboli (RR 1.88; 95% CI, 1.77 to 3.01). Tamoxifen had no effect on secondary malignancies other than endometrial and gastrointestinal cancers (RR 0.96; 95% CI, 0.81 to 1.13). In contrast, tamoxifen significantly decreased myocardial infarction deaths (RR 0.62; 95% CI, 0.41 to 0.93) and was associated with a statistically insignificant decrease in myocardial infarction incidence (RR 0.90; 95% CI, 0.66 to 1.23). Postmenopausal women had greater risk increases for neoplastic outcomes.∖

CONCLUSIONS:  This meta-analysis of randomized trials found tamoxifen use to be significantly associated with several neoplastic and vascular outcomes. Consideration of tamoxifen use requires balance of potential benefits and risks.