Quantification of Ki67 Change as a Valid Prognostic Indicator of Luminal B Type Breast Cancer After Neoadjuvant Therapy

Introduction: Ki67 value and its variation before and after neoadjuvant chemotherapy are commonly tested in relation to breast cancer patient prognosis. This study aims to quantify the extent of changes in Ki67 proliferation pre- and post-neoadjuvant chemotherapy, confirm an optimal cut-off point, and evaluate its potential value for predicting survival outcomes in patients with different molecular subtypes of breast cancer.Methods: This retrospective real-world study recruited 828 patients at the Department of Breast Surgery of the First Affiliated Hospital of China Medical University and the Cancer Hospital of China Medical University from Jan 2014 to Nov 2020. Patient demographic features and disease pathology characteristics were recorded, and biomarkers were verified through immunohistochemistry. Various statistical methods were used to validate the relationships between different characteristics and survival outcomes irrespective of disease-free and overall survival.Results: Among 828 patients, statistically significant effects between pathological complete response and survival outcome were found in both HER2-enriched and triple-negative breast cancer (p < 0.05) but not in Luminal breast cancer (p > 0.05). Evident decrease of Ki67 was confirmed after neoadjuvant chemotherapy. To quantify the extent of Ki67 changes between pre- and post-NAC timepoints, we adopted a computational equation termed Delta Ki67% for research. We found the optimal cut-off value to be Delta Ki67% = -63% via the operating characteristic curve, defining Delta Ki67% <= -63% as positive status and Delta Ki67% > -63% as negative status. Patients with positive Delta Ki67% status were 37.1% of the entire cohort. Additionally, 4.7, 39.9, 34.5 and 39.6% of patients with Luminal A, Luminal B, HER2-enriched and triple negative breast cancer were also validated with positive Delta Ki67% status. The statistically significant differences between Delta Ki67% status and prognostic outcomes were confirmed by univariate and multivariate analysis in Luminal B (univariate and multivariate analysis: p < 0.05) and triple negative breast cancer (univariate and multivariate analysis: p < 0.05). We proved Delta Ki67% as a statistically significant independent prognostic factor irrespective of disease-free or overall survival among patients with Luminal B and triple-negative breast cancer.Conclusions: Delta Ki67% can aid in predicting patient prognostic outcome, provide a measurement of NAC efficacy, and assist in further clinical decisions, especially for patients with Luminal B breast cancer.

Automated summary

This study aimed to quantify changes in Ki67 proliferation before and after neoadjuvant chemotherapy, establish an optimal cut-off point, and evaluate its predictive value for survival outcomes in different molecular subtypes of breast cancer. Results showed significant effects between pathological complete response and survival outcomes in HER2-enriched and triple-negative breast cancer, while a decrease in Ki67 was confirmed post-chemotherapy. The Delta Ki67% was identified as a significant independent prognostic factor for patients with Luminal B and triple-negative breast cancer.