Abstract P3-11-30: Low Ki67 is associated with a lower pathological complete response rate after neoadjuvant therapy in HER2-positive breast cancer patients

Abstract Introduction: The expression of the Ki67 protein assessed by immunohistochemistry (IHC) can estimate the cell proliferation rate and, therefore, be used as a prognostic biomarker to stratify breast cancer patients who harbor a high risk of disease relapse and can benefit more from chemotherapy. However, the prognostic and predictive value of Ki67 for HER2-positive breast cancer is not clearly understood. This study aimed to test the relationship between Ki67 expression and the pathological response in HER2-positive breast cancer. Materials and Methods: We included 260 patients with HER2-positive breast cancer treated with neoadjuvant chemotherapy plus anti-HER2 therapy at A. C. Camargo Cancer Center, Brazil, from January 2010 to December 2022. Information regarding demographics, comorbidities, immunohistochemical features, treatment, clinical staging, and toxicity was collected from patients’ electronic medical records. Ki67 expression information was collected from pathological reports and categorized as <30% or >30%. Descriptive statistics were used to summarize data. Multivariate analysis using Cox’s regression models was performed to integrate factors associated with pathological complete response(pCR). Results: The number of stage II and III patients was 154 (58.3%) and 93 (35.2%), respectively. Histological grade II and III were observed in 136 (51.5%) and 121 (45.8%) tumors. Ki67 >30% was seen in 185 (70%) tumors, and 172 (65.2%) had hormonal receptor expression. The median follow-up was 41 months (37.13-44.87). One-hundred and forty-four (55.4%) patients achieved pCR. The Ki67 <30% was significantly associated with a lower rate of pCR, 33 patients (42.3%) compared to 111 patients (61%) in the group with Ki67>30% (p=0.002). On the multivariate analysis, after adjustment for the use of neoadjuvant trastuzumab plus pertuzumab, use of neoadjuvant anthracyclines, and HER2 score + 3 on IHC (vs. HER2 amplified by FISH/ISH), Ki67 remained as an independent factor associated with pCR. Conclusion: Tumors with Ki67 <30 were associated with a lower rate of pCR after completing neoadjuvant treatment. Ki67 was kept as an independent predictor for pCR regardless of the use of neoadjuvant antracycline or trastuzumab plus pertuzumab, and HER2 score as evaluated by IHC. In the future, PAM 50 or another multigenic test may better fit these patients into different prognostic subgroups and help to de-escalate treatment. Citation Format: Brunna Silva, Mario Machado Lopes, Vladmir Claudio Cordeiro de Lima, Solange Moraes Sanches, Cynthia Aparecida Bueno de Toledo Osório, Marina de brot, Victor Gabriel Bertoli, Guilherme Rossato de Almeida, Carolina Campanholo Marques, Nathália Machado Soldi, José Reinaldo de Oliveira Junior, Mila Meyer Campos Kraychete, Marcelle Goldner Cesca. Low Ki67 is associated with a lower pathological complete response rate after neoadjuvant therapy in HER2-positive breast cancer patients [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-11-30.