Intervention clinical trials are under way to address whether tamoxife
n can prevent breast cancer development. This effort is based on labor
atory evidence that tamoxifen interferes with the initiation and promo
tion of mammary cancer, clinical evidence of decreased breast cancer i
ncidence in the opposite breast of women participating in tamoxifen ad
juvant breast cancer trials, and a favorable toxicity profile of tamox
ifen providing reasonable assurance of drug safety when used in a popu
lation without cancer. The apparently favorable effects of tamoxifen o
n lipid metabolism and bone mineral density provide additional impetus
to this evaluation. Potentially life threatening toxicity of thromboe
mbolism and development of a second cancer remain concerns. With respe
ct to implications of such clinical trials, even upon successful study
completion, difficult issues will remain; these issues include the po
tential for interaction between tamoxifen and dietary fat reduction (a
lso proposed as potential breast cancer prevention), the cost and cost
-effectiveness of wide scale (or selective) implementation of positive
results, and the generalizability of study results to socioeconomical
ly disadvantaged and racial and ethnic minority populations that histo
rically have been under-represented in medical clinical trials. These
important issues should be addressed concurrently as large-scale preve
ntion trials go forward to optimize the practical utility of efficacy
data obtained.