Evaluation of predictive and prognostic value of androgen receptor expression in breast cancer subtypes treated with neoadjuvant chemotherapy

BACKGROUND: Neoadjuvant chemotherapy is the standard treatment for local advanced breast cancer administered to shrink tumors and destroy undetected metastatic cells, thereby facilitating subsequent surgery. Previous studies have shown that AR may be used as a prognostic predictor in breast cancers, but its role in neoadjuvant therapy and the relationship with prognosis of different molecular subtypes of breast cancer need to be further explored. METHODS: We retrospectively evaluated 1231 breast cancer patients with complete medical records at Tianjin Medical University Cancer Institute and Hospital who were treated with neoadjuvant chemotherapy between January 2018 to December 2021. All the patients were selected for prognostic analysis. The follow-up time ranged from 12 to 60 months. We first analyzed the AR expression in different subtypes of breast cancer and its correlation with clinicopathological features. Meanwhile, the association of AR expression and pCR of different breast cancer subtypes was investigated. Finally, the effect of AR status on the prognosis of different subtypes of breast cancer after neoadjuvant therapy was analyzed. RESULTS: The positive rates of AR expression in HR + /HER2-, HR + /HER2 +, HR-/HER2 + and TNBC subtypes were 82.5%, 86.9%, 72.2% and 34.6%, respectively. Histological grade III (P = 0.014, OR = 1.862, 95% CI 1.137 to 2.562), ER positive expression (P = 0.002, OR = 0.381, 95% CI 0.102 to 0.754) and HER2 positive expression (P = 0.006, OR = 0.542, 95% CI 0.227 to 0.836) were independent related factors for AR positive expression. AR expression status was associated with pCR rate after neoadjuvant therapy only in subtype of TNBC. AR positive expression was independent protective factor for recurrence and metastasis in HR + /HER2- (P = 0.033, HR = 0.653, 95% CI 0.237 to 0.986) and HR + /HER2 + breast cancer (P = 0.012, HR = 0.803, 95% CI 0.167 to 0.959), but was independent risk factors for recurrence and metastasis in TNBC (P = 0.015, HR = 4.551, 95% CI 2.668 to 8.063). AR positive expression is not an independent predictor of HR-/HER2 + breast cancer. CONCLUSIONS: AR expressed the lowest in TNBC, but it could be a potential marker for the prediction of pCR in neoadjuvant therapy. AR negative patients had a higher pCR rate. AR positive expression was an independent risk factor for pCR in TNBC after neoadjuvant therapy (P = 0.017, OR = 2.758, 95% CI 1.564 to 4.013). In HR + /HER2- subtype and in HR + /HER2 + subtype, the DFS rate in AR positive patients and AR negative patients was 96.2% vs 89.0% (P = 0.001, HR = 0.330, 95% CI 0.106 to 1.034) and was 96.0% vs 85.7% (P = 0.002, HR = 0.278, 95% CI 0.082 to 0.940), respectively. However, in HR-/HER2 + and TNBC subtypes, the DFS rate in AR positive patients and AR negative patients was 89.0% vs 95.9% (P = 0.102, HR = 3.211, 95% CI 1.117 to 9.224) and 75.0% vs 93.4% (P < 0.001, HR = 3.706, 95% CI 1.681 to 8.171), respectively. In HR + /HER2- and HR + /HER2 + breast cancer, AR positive patients had a better prognosis, however in TNBC, AR-positive patients have a poor prognosis.