BACKGROUND: SHON nuclear expression (SHON-Nuc(+)) was previously reported to predict clinical outcomes to tamoxifen therapy in ER alpha(+) 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 alpha(- )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 alpha(+) 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 ERa(- )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 (1.05-2039), 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 alpha status and SHON-Nuc(+) (p = 0.005), and between SHON-Nuc(+) and tamoxifen therapy (p = 0.007), were both statistically significant.
CONCLUSION: SHON-Nuce(+) in tumours predicts response to tamoxifen in ER alpha+ BC while SHON-Cyto(+) predicts response to ACT.
[1]Univ Nottingham, Dept Clin Oncol, Nottingham, England;
[2]Nottingham Univ Hosp NHS Trust, Nottingham, England;
[3]Menoufia Univ, Natl Liver Inst, Menoufyia, Egypt;
[4]Auckland City Hosp, Auckland, New Zealand;
[5]Northeast Normal Univ, Inst Genet & Cytol, Changchun, Jilin, Peoples R China;
[6]Northeast Normal Univ, MOE, Key Lab Mol Epigenet, Changchun, Jilin, Peoples R China;
[7]Tianjin Med Univ, Dept Bone & Soft Tissue Tumors, Canc Inst & Hosp, Tianjin, Peoples R China;
[8]Fudan Univ, Shanghai Canc Ctr, Shanghai, Peoples R China;
[9]Fudan Univ, Canc Inst, Key Lab Breast Canc Shanghai, Inst Biomed Sci,Shanghai Med Coll, Shanghai, Peoples R China;
[10]Zhengzhou Normal Univ, Lab Mol Biol, Zhengzhou, Henan, Peoples R China;
[11]Chinese Acad Sci, Inst Genet & Dev Biol, Beijing, Peoples R China;
[12]Zhejiang Canc Hosp, Dept Med Oncol, Hangzhou, Zhejiang, Peoples R China;
[13]Auckland Univ Technol, Fac Hlth & Environm Sci, Ctr Biomed & Chem Sci, Sch Sci, Auckland, New Zealand;
[14]Univ Auckland, Liggins Inst, Auckland, New Zealand;
[15]Univ Nottingham, Nottingham City Hosp, Sch Med, Nottingham Breast Canc Res Ctr,Div Canc & Stem Ce, Nottingham, England;
[16]Univ Nottingham, Nottingham Univ Hosp NHS Trust, Sch Med, Dept Histopathol, Nottingham, England;
[17]Tsinghua Univ, Tsinghua Berkeley Shenzhen Inst, Shenzhen, Guangdong, Peoples R China;
[18]ASTAR, Biomed Sci Inst, Lab P53, Singapore, Singapore
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