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. 2023 Apr;12(8):9363-9372.
doi: 10.1002/cam4.5693. Epub 2023 Feb 16.

Prognostic analysis of three forms of Ki-67 in patients with breast cancer with non-pathological complete response before and after neoadjuvant systemic treatment

Weiwei Zhang  1 , Yinggang Xu  1 , Ye Wang  1 , Jinzhi He  1 , Rui Chen  1 , Xinyu Wan  1 , Wenjie Shi  1 , Xiaofeng Huang  1 , Xiaoqing Shi  1 , Jue Wang  1 , Xiaoming Zha  1   2
Affiliations

Prognostic analysis of three forms of Ki-67 in patients with breast cancer with non-pathological complete response before and after neoadjuvant systemic treatment

Weiwei Zhang et al. Cancer Med. 2023 Apr.

Abstract

Background: Patients who do not achieve a pathological complete response (pCR) after neoadjuvant systemic treatment (NST) have a significantly worse prognosis. A reliable predictor of prognosis is required to further subdivide non-pCR patients. To date, the prognostic role in terms of disease-free survival (DFS) between the terminal index of Ki-67 after surgery (Ki-67T ) and the combination of the baseline Ki-67 at biopsy before NST (Ki-67B ) and the percentage change in Ki-67 before and after NST (Ki-67C ) has not been compared.

Aim: This study aimed to explore the most useful form or combination of Ki-67 that can provide prognostic information to non-pCR patients.

Patients and methods: We retrospectively reviewed 499 patients who were diagnosed with inoperable breast cancer between August 2013 and December 2020 and received NST with anthracycline plus taxane.

Results: Among all the patients, 335 did not achieve pCR (with a follow-up period of ≥1 year). The median follow-up duration was 36 months. The optimal cutoff value of Ki-67C to predict a DFS was 30%. A significantly worse DFS was observed in patients with a low Ki-67C (p < 0.001). In addition, the exploratory subgroup analysis showed relatively good internal consistency. Ki-67C and Ki-67T were considered as independent risk factors for DFS (both p < 0.001). The forecasting model combining Ki-67B and Ki-67C showed a significantly higher area under the curve at years 3 and 5 than Ki-67T (p = 0.029 and p = 0.022, respectively).

Conclusions: Ki-67C and Ki-67T were good independent predictors of DFS, whereas Ki-67B was a slightly inferior predictor. The combination of Ki-67B and Ki-67C is superior to Ki-67T for predicting DFS, especially at longer follow-ups. Regarding clinical application, this combination could be used as a novel indicator for predicting DFS to more clearly identify high-risk patients.

Keywords: breast cancer; cell cycle; neoadjuvant chemotherapy; prognosis.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

FIGURE 1
FIGURE 1
Study design and patient flow. B, baseline; C, percentage change; DFS, disease‐free survival; NST, neoadjuvant systemic treatment; pCR, pathological complete response; T, terminal.
FIGURE 2
FIGURE 2
Subgroup analysis of disease‐free survival related to Ki‐67C among non‐pCR patients. B, baseline; C, percentage change; CI, confidence interval; HR, hormone receptor; Non‐pCR, not achieved pathological complete response; TN, triple‐negative (HR−/HER2−).
FIGURE 3
FIGURE 3
Kaplan–Meier survival curve for disease‐free survival by Ki67B (A), Ki67C (B), and combination of Ki‐67B and K‐67C (C, D). B, baseline; C, percentage change; CI, confidence interval; low Ki‐67B = Ki‐67B ≤ 30%; high Ki‐67B = Ki‐67B > 30%; low Ki‐67C = Ki‐67C increased or ≤ 30% reduction; high Ki‐67C = Ki‐67C > 30% reduction.
FIGURE 4
FIGURE 4
Time‐dependent ROC curve analysis for the Cox regression models at year 1 (A), 3 (B), and 5 (B). AUC, area under the curve; B, baseline; C, percentage change; ROC, receiver operating characteristic; T, terminal.
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