The predictive role of Ki67 in pathological complete response (pCR) and invasive disease-free survival (IDFS) in HER2-positive breast cancer: a bi-centric retrospective cohort study of 244 cases.

PURPOSE: The purpose of this study was to examine whether Ki67-scores have a predictive significance for pathological complete response (pCR) and invasive disease-free survival (IDFS) in HER2-positive breast cancer. METHODS: This retrospective, bi-centric cohort study focused on HER2-positive early breast cancer patients undergoing neoadjuvant chemotherapy from 2015 to 2023. Multivariable logistic regression was used to find independent association between various clinical parameters, including Ki67, and pCR. Ki67-values were categorized into three groups (low ≤ 15%, intermediate 15-35%, high > 35%). Kaplan-Meier estimator calculated differences in IDFS. RESULTS: The study included 244 patients with known Ki67-expression. 147 patients (60.3%) achieved pCR. When categorized, 18 (7.4%) were Ki67 low, 114 (46.7%) Ki67 intermediate and 112 (45.9%) Ki67 high. No correlation between Ki67-score as continuous variable and pCR was observed (p = 0.25). HER2 immunohistochemistry (IHC) score 3 + significantly increased pCR compared to IHC score 2 + (63.2% vs. 45%, p = 0.031). Hormone receptor (HR)-positive tumors had a lower pCR rate (53.1% vs. 74.4%, p = 0.001) compared to HR-negative tumors. 5-year IDFS showed no difference between low Ki67 (88.9%; 95% CI 75.5-100%), intermediate Ki67 (82.0%; 95% CI 72.6-92.7%), and high Ki67 (80.9%, 95% CI 70.1-92.3%) subgroups (p = 0.7). CONCLUSION: In HER2-positive breast cancer, the Ki67-score showed no association with either pCR or IDFS, thereby questioning its clinical utility. Conversely the HER2 IHC-score and HR-status were predictive indicators for achieving pCR. Clinical decisions in patients with early HER2-positive breast cancer should not be influenced by Ki67-scores, especially not by using cut-offs.