Systematic review: comparative effectiveness of medications to reduce risk for primary breast cancer.
BACKGROUND
Trials demonstrate the efficacy of medications to reduce the risk for invasive breast cancer.


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


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


METHODS
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.


METHODS
Two reviewers assessed study data, quality, and applicability.


RESULTS
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 per 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 per 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 per 1000 women per year and causes cataracts compared with raloxifene. Tibolone causes strokes in older women.


CONCLUSIONS
Bias, trial heterogeneity, and a dearth of 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.


CONCLUSIONS
Three medications reduce risk for primary breast cancer but increase risk for thromboembolic events (tamoxifen, raloxifene), endometrial cancer (tamoxifen), or stroke (tibolone).
Nelson
Heidi D
HD
Oregon Health & Science University, Veterans Affairs Medical Center, Portland, OR 97239-3098, USA. nelsonh@ohsu.edu
Fu
Rongwei
R
Griffin
Jessica C
JC
Nygren
Peggy
P
Smith
M E Beth
ME
Humphrey
Linda
L
D001943:Breast Neoplasms / Q000517:prevention & control*; D016889:Endometrial Neoplasms / Q000139:chemically induced; D020847:Estrogen Receptor Modulators / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control; D006801:Humans; D009652:Norpregnenes / Q000009:adverse effects / Q000627:therapeutic use*; D020849:Raloxifene Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use*; D020521:Stroke / Q000139:chemically induced; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D013923:Thromboembolism / Q000139:chemically induced
D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride; C027385:tibolone