ReviewPreclinical breast effects of a tissue selective estrogen complex (TSEC) including conjugated estrogen with bazedoxifene

- Conjugated equine estrogens (CEE) exert differential effects on normal and cancerous breast tissues in animal models.
- CEE stimulates mouse uterus to the levels induced by estradiol (E2) but does not stimulate growth of MCF-7 xenograft in nude mice.
- Bazedoxifene (BZA) blocks the effects of both CEE and E2 on uterus and the effect of E2 on breast tumors.
- The tissue selective estrogen complex composed of CEE and BZA could become a safer regimen for menopausal hormone therapy.

The first tissue-selective estrogen complex (TSEC), consisting of a combination of a conjugated equine estrogen (CEE) and bazedoxifene (BZA), has been approved for treatment of the menopause in the USA and European Union. We have postulated that this TSEC might block the estrogenic effects of CEE on breast tissue and thereby prevent breast cancer growth. This manuscript, representing a presentation at a Festschrift honoring Evan Simpson, reviews our published data BZA blocked the in vitro effects of both estradiol and CEE on cell growth and gene expression in MCF-7 cells. BZA completely blocked CEE- or E2-stimulated ductal and terminal end bud growth of immature murine mammary glands and the growth of experimental breast cancers. These findings provide a rationale for future clinical studies to determine whether this TSEC prevents the growth of occult breast cancer in women.