Prospective Explore of Clinical-Pathological Shrinkage Modes After Neoadjuvant Therapy in Breast Cancer
Authors: Bi Zhao , Zhang Zhao-Peng , Xu Cheng-Jun , Chen Peng , Qiu Peng-Fei , Zhao Tong , Wang Yong-Sheng 
Published: October 2021

Abstract
Purpose: The aim was to explore the clinical-pathological shrinkage modes which oriented by breast conserving surgery (BCS) purpose after neoadjuvant therapy (NAT) using three-dimensional (3D) MRI and pathology reconstruction, in order to guide the individualized selection of BCS candidates and scope of resection after NAT. Methods: From April 2014 to 2018, 104 breast cancer patients underwent operation after NAT were included in this prospective study. All patients underwent MRI examinations before and after NAT. Breast residual tumors were prepared with sub-serial section. The 3D MRI and pathology models were reconstructed with 3D-DOCTOR software. The association and correlation between 3D MRI and pathology models were assessed. The traditional shrinkage modes included the surgical pathology complete response, solitary lesions without surrounding lesions, multinodular lesions, solitary lesions with adjacent spotty lesions and diffuse lesions. Combined with the MD Anderson Cancer Center BCS indications after NAT and traditional shrinkage modes, we derived clinical-pathological shrinkage modes which oriented by BCS purpose: clinical pathological-concentric shrinkage modes (CP-CSM) and clinical pathological-non concentric shrinkage modes (CP-NCSM). The CP-CSM means the longest diameter of residual tumor was less than 50% and ≤2cm in comparison with the primary tumor before NAT. Other shrinkage modes were classified as CP-NCSM. Univariate and multivariate logistic regression analysis was conducted to identify the independent predictive factors of clinical-pathological shrinkage modes. A nomogram was developed based on variables in the final model with p<0.05. Results: Based on the gold standard of 3D pathology reconstruction model-measured shrinkage modes, the accuracy, sensitivity and specificity of 3D MRI reconstruction for predicting the traditional shrinkage modes were 84.6%, 61.9% and 90.4%, respectively (Kappa value=0.497). The accuracy, sensitivity and specificity of 3D MRI reconstruction in predicting clinical-pathological shrinkage modes were 93.3%, 97.0% and 86.5%, respectively (Kappa value=0.850). Multivariate analysis showed that primary tumor stage (OR=2.059, 95%CI: 1.187-3.574), mammographic malignant calcification (OR=3.424, 95%CI: 1.437-8.161), molecular subtypes (OR=0.530, 95%CI: 0.364-0.772) and nodal down-staging after NAT (OR=0.183, 95%CI: 0.067-0.497) were independent predictors of clinical-pathological shrinkage modes (all p<0.05). A nomogram was created based on these four predictors. The AUC value was 0.833 (95％CI: 0.710-0.922). The calibration curve showed a satisfactory fit between the predictive and actual observation. With a median follow-up time of 77 months, the recurrence/metastasis rate in the CP-CSM and CP-NCSM group was 7.1% and 29.4%, respectively (p=0.002). Patients with CP-CSM had a better overall survival and disease-free survival (all p<0.05).Conclusion: The 3D MRI reconstruction after NAT could accurately predict the extent of residual tumor. Combining clinical, imaging, molecular subtypes and NAT efficacy, the nomogram of clinical-pathological shrinkage modes showed sufficient predicting accuracy. And it could help to guide the individualized selection of BCS candidates and scope of resection after NAT, thereby achieve the minimum and effective treatment. However, the applicability of the nomogram still needs to be externally validated. Patients with CP-NCSM after NAT had a worse prognosis.