The predictive role of Ki67 in pathological complete response (pCR) and invasive disease-free survival (IDFS) in HER2-positive breast cancer: A retrospective study of 246 cases.

e12610 Background: While Ki67 is a routine diagnostic measure for early hormone receptor positive breast cancer, it is not integrated into the standard procedure for patients with Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer patients, given the substantial risk linked to HER2 expression alone. Consequently, the predictive significance of Ki67 in achieving pathological complete response (pCR) or invasive disease-free survival (IDFS) in this subgroup remains uncertain. Methods: This retrospective, bi-centric analysis focused on HER2-positive early breast cancer patients undergoing neoadjuvant chemotherapy from 2015 to 2023. We assessed the correlation between Ki67 values and the achievement of pathological complete response (pCR, defined as ypT0/is, pN0). Multivariable logistic regression analyzed the independent association of various clinical parameters, including Ki67, with pCR. Ki67 values were categorized into risk groups (low 35%) following the GepardTrio data 1. Kaplan-Meier estimator calculated differences in overall and invasive disease-free survival. Results: The study included 246 HER2-positive early breast cancer patients with known Ki67 expression, followed for a median of 42 months. The median age was 52 years. Final nodal status was pN0 in 80.5%, pN1 in 15%, and pN2 in 3.3%. Hormone receptor positivity was observed in 66% of patients. 147 patients (60%) achieved pCR. Median Ki67 was 30. When categorized, 13% were low, 41.5% intermediate, and 45.5% high risk. No correlation between Ki67 and pCR was observed (p=0.25). HER2 IHC score 3+ significantly increased pCR compared to IHC 2+ (62.2% vs. 44.6%, p=0.023). Hormone receptor-positive tumors had a lower pCR rate (52.7% vs. 72.4%, p=0.0016. 5-year overall survival was 96.5% for pCR and 83.8% for non-pCR (p=0.008). 5-year invasive disease-free survival showed no difference between low Ki67 (89.5%), intermediate Ki67 (79.9%), and high Ki67 (80.9%) groups (p=0.77). Conclusions: In this study, Ki67 did not predict pCR in HER2-positive breast cancer, providing no additional clinical value. HER2 IHC score and hormone receptor status were predictive indicators for pCR. Ki67 expression appears to lack additional value in HER2-positive breast cancer, considering resource implications. 1. Denkert C et al: Ann Oncol. 2013 Nov;24(11):2786-93. doi: 10.1093/annonc/mdt350. Epub 2013 Aug 22. PMID: 23970015.