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

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.