Traditional menopausal hormone therapy containing estrogens/progestin has been 
associated with an increased risk of breast cancer, and estrogen exposure is 
known to promote growth and proliferation of a majority of breast cancers. 
Therefore, it is important for clinicians to consider the breast safety profile 
of any hormone-based therapy used in postmenopausal women. This review provides 
an overview of the breast safety and tolerability profiles of currently marketed 
selective estrogen receptor modulators, antiestrogens, and the first tissue 
selective estrogen complex combining conjugated estrogens with the selective 
estrogen receptor modulator bazedoxifene in postmenopausal women. Selective 
estrogen receptor modulators and antiestrogens act as estrogen receptor 
antagonists in the breast. Tamoxifen, toremifene, and the selective estrogen 
receptor degrader fulvestrant are used to treat breast cancer, and tamoxifen and 
raloxifene protect against breast cancer in high-risk women. Postmenopausal 
women using selective estrogen receptor modulators for prevention or treatment 
of osteoporosis (raloxifene, bazedoxifene) can be reassured that these hormonal 
treatments do not adversely affect their risk of breast cancer and may, in the 
case of raloxifene, even be protective. There are limited data on breast cancer 
in women who use ospemifene for dyspareunia. Conjugated estrogens/bazedoxifene 
use for up to two years did not increase mammographic breast density or breast 
pain/tenderness, and there was no evidence of an increased risk of breast 
cancer, suggesting that conjugated estrogens/bazedoxifene has an improved breast 
safety profile compared with traditional menopausal hormone therapies. Future 
research will continue to focus on development of selective estrogen receptor 
modulators and selective estrogen receptor modulator combinations capable of 
achieving the ideal balance of estrogen receptor agonist and antagonist effects.