Abstract: Objective To investigate the pathological changes of uterus in nude mice with breast cancer xenograft treated with tamoxifen (TAM), and effect of progesterone treatment on the proliferation of breast cancer and therapeutic efficacy of tamoxifen. Methods Prospective, randomized, placebo-controlled four-arm study in xenotransplantations:MCF7 cells were injected into nude mice. Estradiol (E2) pellets were implanted. After 43 days, the breast cancer xenograft was treated with progesterone (P) or TAM or TAM plus P or placebo. All four groups (6 mice/group) were further monitored for 56 days. After 56 days, the mice were sacrificed and take the tumor and uterus. Fresh tissue was immediately stored in 4% paraformaldehyde for hematoxylin and eosin (HE) staining and tumor growth curve mapping.Results Tumor growth curve showed that progesterone group did not promote additional proliferation of breast cancer compared with placebo group (P>0.05). Breast cancer tissue volume decreased significantly after tamoxifen treatment (P<0.01). The HE staining result showed that the tumor tissue was loose connective and the number of tumor cells decreased. Endometrium HE staining showed that the number of glands increased, and glands cells were hyperchromatic, some of which presented atypia and pathological results of endometrial dysplasia. Compared with the placebo group, the number of endometrial glands increased significantly after tamoxifen treatment (P<0.01), while that of the progesterone group did not increase (P>0.05). Conclusion In the nude mice with breast cancer, the tumor volume was significantly reduced after tamoxifen treatment, but the glands were increased, indicating endometrial dysplasia. Progesterone alone did not promote the obvious proliferation of xenotransplantations, without obvious endometrial hyperplasia, Therefore the application of progesterone did not significantly antagonize tamoxifen.

Key words: tamoxifen, nude mice, breast cancer xenograft, hormone therapy, endometrium