@article { , title = {SHON expression predicts response and relapse risk of breast cancer patients after anthracycline-based combination chemotherapy or tamoxifen treatment}, abstract = {BACKGROUND: SHON nuclear expression (SHON-Nuc+) was previously reported to predict clinical outcomes to tamoxifen therapy in ER?+ breast cancer (BC). Herein we determined if SHON expression detected by specific monoclonal antibodies could provide a more accurate prediction and serve as a biomarker for anthracycline-based combination chemotherapy (ACT). METHODS: SHON expression was determined by immunohistochemistry in the Nottingham early-stage-BC cohort (n=1,650) who, if eligible, received adjuvant tamoxifen; the Nottingham ER?- early-stage-BC (n=697) patients who received adjuvant ACT; and the Nottingham locally advanced-BC cohort who received pre- operative ACT with/without taxanes (Neo-ACT, n=120) and if eligible, 5-year adjuvant tamoxifen treatment. Prognostic significance of SHON and its relationship with the clinical outcome of treatments were analysed. RESULTS: As previously reported, SHON-Nuc+ in high risk/ER?+ patients was significantly associated with a 48\% death risk reduction after exclusive adjuvant tamoxifen treatment compared with SHON-Nuc- [HR(95\%CI)=0.52(0.34-0.78), p=0.002]. Meanwhile, in ER?- patients treated with adjuvant ACT, SHON cytoplasmic expression (SHON-Cyto+) was significantly associated with a 50\% death risk reduction compared with SHON-Cyto- [HR(95\%CI)=0.50(0.34-0.73), p=0.0003]. Moreover, in patients received Neo-ACT, SHON-Nuc- or SHON-Cyto+ was associated with an increased pathological complete response (pCR) compared with SHON-Nuc+ [21\% vs 4\%; OR(95\%CI)=5.88(1.28-27.03), p=0.012], or SHON-Cyto- [20.5\% vs 4.5\%; OR(95\%CI)=5.43(1.18-25.03), p=0.017], respectively. After receiving Neo-ACT, patients with SHON-Nuc+ had a significantly lower distant relapse risk compared to those with SHON-Nuc- [HR(95\%CI)=0.41(0.19-0.87), p=0.038], whereas SHON-Cyto+ patients had a significantly higher distant relapse risk compared to SHON-Cyto- patients [HR(95\%CI)=4.63(1.05-20.39), p=0.043]. Furthermore, multivariate Cox regression analyses revealed that SHON-Cyto+ was independently associated with a higher risk of distant relapse after Neo-ACT and 5- year tamoxifen treatment [HR(95\%CI)=5.08(1.13-44.52), p=0.037]. The interaction term between ER? status and SHON-Nuc+ (p=0.005), and between SHON-Nuc+ and tamoxifen therapy (p=0.007), were both statistically significant. CONCLUSION: SHON-Nuc+ in tumours predicts response to tamoxifen in ER?+ BC while SHON-Cyto+ predicts response to ACT.}, doi = {10.1038/s41416-019-0405-x}, eissn = {1532-1827}, issn = {0007-0920}, issue = {7}, journal = {British Journal of Cancer}, pages = {728–745}, publicationstatus = {Published}, publisher = {Cancer Research UK}, url = {https://nottingham-repository.worktribe.com/output/1499279}, volume = {120}, keyword = {Nottingham Breast Cancer Research Centre, Cancer Research, Oncology}, year = {2019}, author = {Abdel-Fatah, Tarek M.A. and Broom, Reuben J. and Lu, Jun and Moseley, Paul M. and Huang, Baiqu and Li, Lili and Liu, Suling and Chen, Longxin and Ma, Runlin Z and Cao, Wenming and Wang, Xiaojia and Li, Yan and Perry, Jo K. and Aleskandarany, Mohammed and Nolan, Christopher C and Rakha, Emad A and Lobie, Peter E and Chan, Stephen Y.T. and Ellis, Ian O and Hwang, Le-Ann and Lane, David P and Green, Andrew R and Liu, Dong-Xu} }