SHON expression predicts response and relapse risk of breast cancer patients after anthracycline-based combination chemotherapy or tamoxifen treatment
Menée à partir de l'analyse immunohistochimique d'échantillons tumoraux prélevés sur 1 650 patientes atteintes d'un cancer du sein de stade précoce, cette étude met en évidence une association entre l'expression de la protéine SHON et le risque de récidive ou la réponse à un traitement par anthracyclines ou tamoxifène
Background : SHON nuclear expression (SHON-Nuc+) was previously reported to predict clinical outcomes to tamoxifen therapy in ER
α+ 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
α
− 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
α+ 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
α
− 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
α 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
α+ BC while SHON-Cyto+ predicts response to ACT.
British Journal of Cancer , résumé, 2019