The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation.
BACKGROUND
Raloxifene hydrochloride is a selective estrogen receptor modulator that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism, and blood clotting.


OBJECTIVE
To determine whether women taking raloxifene have a lower risk of invasive breast cancer.


METHODS
The Multiple Outcomes of Raloxifene Evaluation (MORE), a multicenter, randomized, double-blind trial, in which women taking raloxifene or placebo were followed up for a median of 40 months (SD, 3 years), from 1994 through 1998, at 180 clinical centers composed of community settings and medical practices in 25 countries, mainly in the United States and Europe.


METHODS
A total of 7705 postmenopausal women, younger than 81 (mean age, 66.5) years, with osteoporosis, defined by the presence of vertebral fractures or a femoral neck or spine T-score of at least 2.5 SDs below the mean for young healthy women. Almost all participants (96%) were white. Women who had a history of breast cancer or who were taking estrogen were excluded.


METHODS
Raloxifene, 60 mg, 2 tablets daily; or raloxifene, 60 mg, 1 tablet daily and 1 placebo tablet; or 2 placebo tablets.


METHODS
New cases of breast cancer, confirmed by histopathology. Transvaginal ultrasonography was used to assess the endometrial effects of raloxifene in 1781 women. Deep vein thrombosis or pulmonary embolism were determined by chart review.


RESULTS
Thirteen cases of breast cancer were confirmed among the 5129 women assigned to raloxifene vs 27 among the 2576 women assigned to placebo (relative risk [RR], 0.24; 95% confidence interval [CI], 0.13-0.44; P<.001). To prevent 1 case of breast cancer, 126 women would need to be treated. Raloxifene decreased the risk of estrogen receptor-positive breast cancer by 90% (RR, 0.10; 95% CI, 0.04-0.24), but not estrogen receptor-negative invasive breast cancer (RR, 0.88; 95% CI, 0.26-3.0). Raloxifene increased the risk of venous thromboembolic disease (RR, 3.1; 95% CI, 1.5-6.2), but did not increase the risk of endometrial cancer (RR, 0.8; 95% CI, 0.2-2.7).


CONCLUSIONS
Among postmenopausal women with osteoporosis, the risk of invasive breast cancer was decreased by 76% during 3 years of treatment with raloxifene.
Cummings
S R
SR
Department of Medicine, University of California, San Francisco, USA. scummings@psg.ucsf.edu
Eckert
S
S
Krueger
K A
KA
Grady
D
D
Powles
T J
TJ
Cauley
J A
JA
Norton
L
L
Nickelsen
T
T
Bjarnason
N H
NH
Morrow
M
M
Lippman
M E
ME
Black
D
D
Glusman
J E
JE
Costa
A
A
Jordan
V C
VC
D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000378:metabolism; D004311:Double-Blind Method; D016889:Endometrial Neoplasms / Q000453:epidemiology; D004965:Estrogen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D004967:Estrogens / Q000819:agonists*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D017698:Postmenopause; D020849:Raloxifene Hydrochloride; D011960:Receptors, Estrogen / Q000378:metabolism; D012306:Risk; D013923:Thromboembolism / Q000453:epidemiology
D004965:Estrogen Antagonists; D004967:Estrogens; D010880:Piperidines; D011960:Receptors, Estrogen; D020849:Raloxifene Hydrochloride