Clinical Study On The Correlation Between AR Expression Level And Efficacy Of Neoadjuvant Therapy For HER-2 Positive Breast Cancer

Objective(s): To investigate the correlation between different clinical and pathological features with pathological complete response(pCR)rate in HER-2positive breast cancer patients post-neoadjuvant treatment,especially,focusing on the expression of androgen receptor(AR)in HER-2 positive breast cancer and significant difference in pCR rate in HER-2 positive breast cancer patients with different AR expression levels.It was also analysed the efficacy of AR expression levels as a predictor of pCR rates after neoadjuvant therapy for HER-2-positive breast cancer.To find new predictive biomarkers for the efficacy of neoadjuvant therapy in HER-2positive breast cancer patients,so that provide reference for clinicians’ diagnosis and treatment.Methods: Clinicopathological characteristics and postoperative pathological response were collected from HER-2 positive breast cancer patients who received neoadjuvant chemotherapy combined with trastuzumab + pertuzumab targeted therapy from 1 January 2019 to 31 October 2022 in three breast cancer centers in southwest China.The patients were divided into AR low expression group(AR≤70%)and AR high expression group(AR >70%)using the 70% of AR expression level as the cut-off value.1.A chi-square test was used to analyse whether there were differences in each clinicopathological feature between the AR low expression group and the AR high expression group;the correlation between each clinicopathological feature and the pCR rate was analysed univariately;variables with statistical significance in the univariate analysis were substituted into the multi-factor binary logistic regression analysis to determine the independent influencing factors of pCR.2.Further subgroup analysis of the relationship between AR expression levels,ER/AR ratio,PR/AR ratio and pCR rate.3.ROC curves were plotted to assess the accuracy of AR expression levels,ER/AR ratios as predictors of pCR rates.Results: A total of 258 HER-2-positive breast cancer patients were collected according to the inclusion and exclusion criteria,of whom 154 patients(59.69%)achieved pCR on postoperative pathology.In the low AR expression group,153 patients had a pCR rate of 54.25%;in the high AR expression group,105 patients had a pCR rate of 67.62%.1.There was no statistical difference in the clinicopathological feature between the AR high expression and AR low expression groups(P>0.05);the pCR rate was significantly associated with the level of AR expression(P=0.031),clinical staging(P=0.033),estrogen receptor(ER)expression status(P=0.048),and chemotherapy regimen(P=0.034);and the level of AR expression,clinical staging,ER expression and neoadjuvant chemotherapy regimen were all independent influencing factors for pCR;the pCR rate was higher in patients with high AR expression than in those with low AR expression(P=0.031),and the difference was statistically significant.2.In the five subgroups aged ≥50 years,HER-2++,HR-positive,PR-positive,and Ki-67 >20%,the pCR rate was higher in patients with high AR expression than in patients with low AR expression,and the difference was statistically significant;in the subgroup with positive ER and AR,the pCR rate was higher in patients with ER/AR ratio <1 than in patients with ER/AR ratio ≥1(P=0.038),with a statistically significant difference.3.In overall HER-2-positive breast cancer patients,the AUC values(area under ROC curve)of the relationship between AR expression level and ER/AR ratio and pCR rate were 0.5866 and 0.6222,respectively.Conclusion(s):1.HER-2 positive breast cancer patients with high AR expression achieved higher pCR rates in neoadjuvant chemotherapy combined with trastuzumab +pertuzumab-targeted therapy;AR expression levels were an independent influence on pCR rates.2.In HER-2 positive breast cancers that were positive for both ER and AR,patients with an ER/AR ratio <1 had a higher pCR rate than those with an ER/AR ratio ≥1.3.In HER-2 positive breast cancer,the accuracy of AR and the ER/AR ratio in predicting pCR is low and neither can be used as an independent predictor of pCR.In conclusion,this trial demonstrated that AR expression levels were strongly correlated with pCR rates in HER-2 positive breast cancer patients receiving neoadjuvant dual-target therapy.