Prognostic significance of tumour Ki-67 dynamics during neoadjuvant treatment in patients with breast cancer: a population-based cohort studyResearch in context

• Published in: The Lancet Regional Health. Europe
• Main Authors: Maria Angeliki Toli, Xingrong Liu, Davide Massa, Stefania Lando, Caroline Boman, Nikolaos Tsiknakis, Christian Tranchell, Andri Papakonstantinou, Giuseppe Fotia, Claudio Vernieri, Valentina Guarneri, Jonas Bergh, Maria Vittoria Dieci, Louise Eriksson Bergman, Alexios Matikas, Theodoros Foukakis
• Format: Article
• Language: English
• Published: Elsevier 2025-11-01
• Subjects: Breast cancer; Neoadjuvant chemotherapy; Ki-67; Prognosis; Survival; Stratification
• Online Access: http://www.sciencedirect.com/science/article/pii/S2666776225002248
• ISSN: 2666-7762

Summary: Background: Although Ki-67 is a commonly used proliferation marker in breast cancer (BC), its prognostic value after neoadjuvant chemotherapy (NACT) remains unclear. This study aims to investigate the prognostic implications of Ki-67 dynamics during NACT. Methods: Patients with invasive BC treated with NACT (2007–2020) were identified through the National Breast Cancer Register (NBCR). Associations between Ki-67 dynamics with survival outcomes were studied (spline-based Cox regression). The prognostic value of Ki-67 in the Neo-Bioscore model was examined and optimal cut-off values for relative change of Ki-67 ((post-NACT–pre-NACT Ki-67)/pre-NACT Ki-67) were explored (minimum p-value approach). Findings: Among 2494 patients, median pre-NACT Ki-67 was 40% (IQR:28–65%). Median post-NACT Ki-67 in patients with residual disease (n = 1826) was 12% (IQR:5–35%). Lower post-NACT Ki-67 was associated with better breast cancer specific survival (BCSS) in the whole cohort (p < 0.0001), in ER+/HER2− (p = 0.0001) and TNBC (p = 0.0007), but not in HER2+ BC (p = 0.8223). Post-NACT Ki-67 improved the Neo-Bioscore prognostic model increasing the C-index from 0.758 to 0.802. Post-NACT Ki-67, as well as absolute and relative change of Ki-67 were strongly correlated with each other and were prognostic for long-term outcomes. Optimal cut-off values for relative change of Ki-67 identified prognostic subgroups for ER+/HER2− BC (n = 730, p < 0.0001), and TNBC (n = 279, p < 0.0001). The results were validated in an external TNBC cohort of 221 patients (p = 0.00073). Notably, the identified low-risk patients with residual disease and at least 48% reduction of Ki-67 after NACT, had comparable survival to those with pathological complete response (pCR) (p = 0.13). Interpretation: Relative change of Ki-67 was independently prognostic for patient risk stratification. Ki-67 in residual disease warrants for further investigation when exploring post-neoadjuvant treatment strategies. Funding: Cancerfonden, Vetenskapsrådet, Cancerföreningen i Stockholm and Region Stockholm.