Meta-analysis of vascular and neoplastic events associated with tamoxifen.
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.


METHODS
Random effects meta-analysis of published randomized controlled trials.


METHODS
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.


METHODS
Tamoxifen at variable dose and duration.


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.
Braithwaite
R Scott
RS
Section of Clinical Systems Modeling, Division of General Internal Medicine, Department of Medicne, University of Pittsburgh, Pittsburgh, PA 15213, USA. braithwaiters@msx.upmc.edu
Chlebowski
Rowan T
RT
Lau
Joseph
J
George
Suzanne
S
Hess
Rachel
R
Col
Nananda F
NF
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D016889:Endometrial Neoplasms / Q000453:epidemiology / Q000209:etiology; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology* / Q000209:etiology; D011655:Pulmonary Embolism / Q000453:epidemiology / Q000209:etiology; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D020521:Stroke / Q000453:epidemiology / Q000209:etiology; D013629:Tamoxifen / Q000009:adverse effects*; D014652:Vascular Diseases / Q000453:epidemiology* / Q000209:etiology
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen