Temporality of change in Ki67 labelling following neoadjuvant systemic chemotherapy of breast cancer—the common drop often subsides with time

Ki67 immunohistochemistry is widely used in clinical settings to assess tumour proliferation in breast cancer, yet the temporal changes in Ki67 labelling index following neoadjuvant chemotherapy (NACT) are underexplored. Matched core biopsy and surgical excision specimens of invasive breast cancers were collected, and the Ki67 immunostained slides were examined. Ki67 labelling index was determined and statistically evaluated based on the time elapsed between the last cycle of NACT and surgery. Subgroup analyses were carried out based on surrogate molecular subtypes, Residual Cancer Burden (RCB), and European Working Group for Breast Screening Pathology tumour regression (TR) categories. The study included 54 paired breast cancer cases post-NACT. Most tumours were RCB-II (n = 39) and TR2b (n = 20). The average time from NACT completion to surgery was 40.3 days. Of three methods (including image-analysis and sample-counting), eye-balling estimation provided the best linear regression fit (p = 0.003, R² = 0.1548). Subgroup analysis showed reduced proliferation suppression over time in HER2-positive, triple-negative, and luminal B-like tumours, as well as RCB-II, RCB-III, TR2b, TR2c, and TR3 tumour regression categories. Conversely, luminal A-like tumours, RCB-I, and TR2a categories showed an opposite trend, though limited by small sample size. Multiple studies highlight the prognostic value of Ki67 labelling index post-NACT, with pre- and post-treatment values and change between them serving as independent prognosticators, but our data suggest that the latter two may be time-dependent after the completion of NACT. The proliferation-reducing effect of NACT diminishes over time, particularly in non-luminal A-like tumours and those with poorer treatment responses.