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 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.

• Authors: Tarek M A Abdel-Fatah, Reuben J Broom, Jun Lu, Paul M Moseley, Baiqu Huang, Lili Li, Suling Liu, Longxin Chen, Runlin Z Ma, Wenming Cao, Xiaojia Wang, Yan Li, Jo K Perry, Mohammed Aleskandarany, Christopher C Nolan, Emad A Rakha, Peter E Lobie, Stephen Y T Chan, Ian O Ellis, Le-Ann Hwang, David P Lane, Andrew R Green, Dong-Xu Liu
• Journal: British journal of cancer (Br J Cancer) Vol. 120 Issue 7 Pg. 728-745 (04 2019) ISSN: 1532-1827 [Electronic] England
• PMID: 30816325 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthracyclines
• Estrogen Receptor alpha
• Oncogene Proteins
• SHON protein, human
• Tamoxifen

Topics

• Adolescent
• Adult
• Aged
• Anthracyclines (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy, metabolism)
• Carcinoma, Ductal, Breast (drug therapy, metabolism)
• Cell Nucleus (metabolism)
• Chemotherapy, Adjuvant
• Disease-Free Survival
• Estrogen Receptor alpha (metabolism)
• Female
• Humans
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Recurrence, Local (epidemiology)
• Oncogene Proteins (metabolism)
• Prognosis
• Tamoxifen (therapeutic use)
• Young Adult