SHON Expression Predicts Response and Relapse Risk of Breast Cancer Patients After Anthracycline-Based Combination Chemotherapy or Tamoxifen Treatment

SHON Expression Predicts Response and Relapse Risk of Breast Cancer Patients After Anthracycline-Based Combination Chemotherapy or Tamoxifen Treatment
Title:
SHON Expression Predicts Response and Relapse Risk of Breast Cancer Patients After Anthracycline-Based Combination Chemotherapy or Tamoxifen Treatment
Other Titles:
British Journal of Cancer
Publication Date:
01 March 2019
Citation:
Abdel-Fatah, T.M.A., Broom, R.J., Lu, J. et al. SHON expression predicts response and relapse risk of breast cancer patients after anthracycline-based combination chemotherapy or tamoxifen treatment. Br J Cancer 120, 728–745 (2019). https://doi.org/10.1038/s41416-019-0405-x
Abstract:
Background: SHON nuclear expression (SHON-Nuc+) was previously reported to predict clinical outcomes to tamoxifen therapy in ERα+ 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 ERα- 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/ERα+ 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 ERα- 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 ERα 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 ERα+ BC while SHON-Cyto+ predicts response to ACT.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
This work was supported by the Breast Cancer Foundation New Zealand (to D.-X.L. & R.J.B., no grant number), the New Zealand Breast Cancer Cure (to D.-X.L., no grant number), the Health Research Council of New Zealand (14/704 to D.-X.L., R.J.B., T.M.A.A.-F., J.L., A.R.G., S.Y.T.C. & I.O.E.), the Auckland Medical Research Foundation (1113022 to D-X.L.), the Margaret Morley Medical Trust (to D.-X.L., no grant number), the Maurice & Phyllis Paykel Trust (to D.-X.L., no grant number), the Kelliher Charitable Trust (to D.-X.L., no grant number), the Lottery Health Research of New Zealand (340942 to D.-X.L., I.O.E., A.R.G., S.Y.T.C. & T.M.A.A.-F.), the Biopharma Programme of the University of Auckland (to D.-X.L., no grant number), and the Shenzhen Development and Reform Commission Subject Construction Project (2017/1434 to P.E.L).
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ISSN:
0007-0920
1532-1827
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