passages.id: 12762
passages.type: title and abstract
passages.text: Inhibitory effects of a bazedoxifene/conjugated equine estrogen combination on human breast cancer cells in vitro.
  Breast cancer incidence is increased in women receiving menopausal hormone therapy with estrogen plus progestin but not with estrogen alone. The use of a tissue-selective estrogen complex (TSEC) has been proposed as a novel menopausal hormone therapy strategy to eliminate the requirement for a progestogen. Combination of bazedoxifene (BZA) with conjugated estrogens (CEs), the first TSEC, has shown beneficial effects. Whether it would exert antiestrogenic effects on breast cancer is not clear. To address this issue, we compared estradiol (E(2)) and CE alone on proliferation and apoptosis in MCF-7 breast cancer cells. CE stimulated growth of MCF-7 cells at a peak concentration 10-fold higher than required for E(2). Both CE and E(2) alone increased DNA synthesis and reduced apoptosis with activation of MAPK, Akt, and p70S6K and up-regulation of antiapoptotic factors survivin, Bcl-2, and X-linked inhibitor of apoptosis protein, These effects could be completely blocked by BZA. Gene expression studies demonstrated that CE and E(2) were equally potent on expression of cMyc, pS2, and WNT1 inducible signaling pathway protein 2, whereas the stimulatory effects of CE on progesterone receptor and amphiregulin expression were weaker than E(2). BZA effectively blocked each of these effects and showed no estrogen agonistic effects when used alone. Our results indicate that the stimulatory effects of E(2) or CE on breast cancer cells could be completely abrogated by BZA. These studies imply that the CE/BZA, TSEC, exerts antiestrogenic effects on breast cancer cells and might block the growth of occult breast neoplasms in postmenopausal women, resulting in an overall reduction in tumor incidence.