Prognostic predictive value of Ki-67 in stage I–II triple-negative breast cancer

Aim: Our research aimed to determine an optimal cutoff value and investigate the prognostic predictive function of Ki-67. Materials & methods: We retrospectively enrolled 1146 patients diagnosed with stage I–II triple-negative breast cancer. Disease-free and overall survival were analyzed using the Kaplan–Meier method and the Cox regression model. Results: We classified Ki-67 >45% as the high group (n = 716). A Ki-67 level of >45% was associated with poorer disease-free survival (p = 0.039) and overall survival (p = 0.029). Lymph node stage, neoadjuvant chemotherapy, and radiotherapy were independent predictive variables of prognosis. Conclusion: Triple-negative breast cancer may be further subcategorized according to the Ki-67 level. Neoadjuvant chemotherapy and postoperative radiotherapy can improve the prognosis of early triple-negative breast cancer. This study aimed to find the best value of Ki-67, which is a marker used in breast cancer. At last, according to the Ki-67 level over 45%, triple-negative breast cancer may be divided into two groups. Based on the level of Ki-67, treatment decisions may be better. However, we still need more studies to confirm this. Triple-negative breast cancer may be further subcategorized according to the Ki-67 level >45%, which is associated with a poorer prognosis. Treatment decisions based on the level of Ki-67 may be more favorable to the prognosis of patients. This research aimed to determine an optimal cutoff value and investigate the prognostic predictive function of Ki-67, which is a proliferation-related biomarker used in luminal breast cancer. We retrospectively enrolled 1146 patients diagnosed with stage I–II triple-negative breast cancer, between Jan 2013 and Dec 2020, at the Sun Yat-sen University Cancer Center. The best cutoff point for Ki-67 was 45%, which was found in the X-tile. For the 1146 patients, we classified Ki-67 >45% as the high group and Ki-67 ≤ 45% as the low group. Lymph node stage, neoadjuvant chemotherapy, and postoperative radiotherapy were independent predictive variables of prognosis. Triple-negative breast cancer may be further subcategorized according to the Ki-67 level >45%, which is associated with a poorer prognosis, particularly in the lymph node-negative group. Neoadjuvant chemotherapy and postoperative radiotherapy can improve the prognosis. Therefore, there is still a need for prospective studies with large sample sizes, specialized assay technicians, and standard operating procedures to explore the optimal detection procedure for Ki-67.研究目的：本研究旨在确定Ki-67（Ki-67）的最佳截断值，并探讨其预后预测价值。Ki-67是一种与细胞增殖相关的生物标志物，最初多用于管腔型乳腺癌的检测。 材料与方法：本研究回顾性纳入2013年1月至2020年12月期间于中山大学肿瘤防治中心确诊的1146例I~II期三阴性乳腺癌（triple-negative breast cancer）患者。采用卡普兰-迈耶（Kaplan–Meier）法与考克斯（Cox）回归模型分析患者的无病生存期与总生存期。通过X-tile软件确定Ki-67的最佳截断值为45%，据此将1146例患者分为Ki-67＞45%的高表达组（n=716）与Ki-67≤45%的低表达组。 研究结果：Ki-67＞45%与较差的无病生存期（p=0.039）及总生存期（p=0.029）显著相关。淋巴结分期、新辅助化疗与术后放疗为患者预后的独立预测因素。进一步亚组分析显示，Ki-67＞45%与不良预后的相关性在淋巴结阴性患者中尤为显著。 研究结论：三阴性乳腺癌可根据Ki-67表达水平进一步细分，Ki-67＞45%的患者预后更差。新辅助化疗与术后放疗可改善早期三阴性乳腺癌患者的预后。基于Ki-67表达水平制定治疗决策或可更有益于患者的预后。本研究仍需开展大样本量的前瞻性研究，并配备专业的检测技术人员与标准化操作流程，以探索Ki-67的最优检测方案。