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Dynamic assessment of proliferation to guide response-adapted therapy in the setting of neoadjuvant chemotherapy in ER+/HER2- breast cancer

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Title: Dynamic assessment of proliferation to guide response-adapted therapy in the setting of neoadjuvant chemotherapy in ER+/HER2- breast cancer
Authors: Saghir, Hani, Veerla, Srinivas, Loman, Niklas, Kimbung, Siker
Contributors: Lund University, Profile areas and other strong research environments, Other Strong Research Environments, LUCC: Lund University Cancer Centre, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Övriga starka forskningsmiljöer, LUCC: Lunds universitets cancercentrum, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Breast/ovarian cancer, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Bröst/ovarialcancer, Originator, Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Translational Cancer Research, Breast/lung cancer, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för translationell cancerforskning, Bröst/lungcancer, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Breast/ovarian cancer, Breast and Ovarian Cancer Genomics, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Bröst/ovarialcancer, Bröst- och ovarialcancer, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section I, Breast/lungcancer, Research Group Lung Cancer, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion I, Bröst/lungcancer, Forskningsgrupp Lungcancer, Originator
Source: Translational Oncology. 63:1-11
Subject Terms: Medical and Health Sciences, Clinical Medicine, Cancer and Oncology, Medicin och hälsovetenskap, Klinisk medicin, Cancer och onkologi
Description: Biomarkers for evaluating response to neoadjuvant chemotherapy (NACT) in ER+/HER2- breast cancer remain limited. This study explores the impact of NACT on tumor proliferation dynamics and its association with relapse-free interval (RFI) among 175 patients with early ER+/HER2- breast tumors. Proliferation was assessed at baseline, after completing two NACT cycles, and in the residual tumor using Ki67 immunohistochemistry (IHC) and two gene expression assays (GEAs): SSP-Ki67 and AURKA score. Slight to moderate agreement was observed between IHC and GEAs, with IHC-Ki67 consistently classifying more tumors as highly proliferative compared to SSP-Ki67 at both baseline and surgery. Proliferation status at baseline was not prognostic for RFI using either IHC-Ki67 or SSP-Ki67 in our cohort. However, patients with persistently high proliferation after two NACT cycles or in the residual tumor following NACT were at increased risk of relapse, with SSP-Ki67 outperforming IHC-Ki67 in identifying patients with a poorer prognosis. Our results demonstrate that tumor proliferation status measured after brief exposure to NACT or in the residual tumor post-NACT holds prognostic value and may inform the tailoring of post-neoadjuvant treatment strategies in patients with early luminal breast cancer, and that relying on IHC-Ki67 to evaluate treatment response may potentially lead to overtreatment.
Access URL: https://doi.org/10.1016/j.tranon.2025.102597
Database: SwePub
Description
Abstract:Biomarkers for evaluating response to neoadjuvant chemotherapy (NACT) in ER+/HER2- breast cancer remain limited. This study explores the impact of NACT on tumor proliferation dynamics and its association with relapse-free interval (RFI) among 175 patients with early ER+/HER2- breast tumors. Proliferation was assessed at baseline, after completing two NACT cycles, and in the residual tumor using Ki67 immunohistochemistry (IHC) and two gene expression assays (GEAs): SSP-Ki67 and AURKA score. Slight to moderate agreement was observed between IHC and GEAs, with IHC-Ki67 consistently classifying more tumors as highly proliferative compared to SSP-Ki67 at both baseline and surgery. Proliferation status at baseline was not prognostic for RFI using either IHC-Ki67 or SSP-Ki67 in our cohort. However, patients with persistently high proliferation after two NACT cycles or in the residual tumor following NACT were at increased risk of relapse, with SSP-Ki67 outperforming IHC-Ki67 in identifying patients with a poorer prognosis. Our results demonstrate that tumor proliferation status measured after brief exposure to NACT or in the residual tumor post-NACT holds prognostic value and may inform the tailoring of post-neoadjuvant treatment strategies in patients with early luminal breast cancer, and that relying on IHC-Ki67 to evaluate treatment response may potentially lead to overtreatment.
ISSN:19365233
DOI:10.1016/j.tranon.2025.102597