Pipendoxifene (ERA-923) is a selective estrogen receptor modulator with a distinct profile compared with tamoxifen. In particular, unlike tamoxifen, ERA-923 is devoid of uterotropic activity and does not stimulate the growth of endometrial tumors in the EnCa-101 (human endometrial adenocarcinoma that is continuously passaged in animals in the presence of estrogen) experimental mice model. These data may indicate that, in patients, ERA-923 will not increase the incidence of endometrial hyperplasia or cancer. ERA-923 inhibits estrogen-stimulated ER-alpha-dependent tumor growth with equal effects compared with tamoxifen in models sensitive to tamoxifen. ERA-923 partially or completely overcomes tamoxifen resistance. In vivo combination of temsirolimus and ERA-923 at certain doses and schedules completely inhibited breast carcinoma growth, while individual agents were only partially effective. Pipendoxifene had been in phase II clinical trial for the treatment of refractory metastatic breast cancer. However, this research has been discontinued.