Tamoxifen,an important endocrine therapeutic agent,is widely used for the treatment of estrogen receptor positive (ER+) breast cancer.However,de novo or acquired resistance prevents patients from benefitting from endocrine approaches and necessitates alteative treatments.In this study,we report that small heat protein beta-8 (HSPB8) may serve as an important molecule in tamoxifen resistance.HSPB8 expression is enhanced in MCF-7 cells resistant to tamoxifen (MCF-7/R) compared to parent cells.Moreover,high expression of HSPB8 associates with poor prognosis in ER+ breast cancer patients but not in patients without classification.Stimulating ER signaling by heterogeneous expression of ERa or 17β-estradiol promotes HSPB8 expression and reduces the cell population in G1 phase.In contrast,blockage of ER signaling by tamoxifen down-regulates the expression of HSPB8.In addition,knocking down HSPB8 by specific siRNAs induces significant cell cycle arrest at G1 phase.AZDS055 was found to be more potent against the proliferation of MCF-7/R cells than that of parent cells,which was associated with down-regulation of HSPB8.We found that the anti-proliferative activity of AZD8055 was positively correlated with the HSPB8 expression level in ER+ breast cancer cells.Thus,AZD8055 was able to overcome tamoxifen resistance in breast cancer cells,and the expression of HSPB8 may predict the efficacy of AZD8055 in ER+ breast cancer.This hypothesis deserves further investigation.