PURPOSE: To evaluate the prognostic significance of changes in pre- and post-neoadjuvant chemotherapy (NACT) Ki67 in patients with primary invasive triple-negative breast cancer (TNBC). METHODS: Population-based registry data were retrieved for patients diagnosed with TNBC between 2007 and 2021 (n = 9262). Multivariable Cox regression analysis was performed for disease-specific survival (DSS) and overall survival (OS) adjusted for age and residual disease in the breast and nodes (RDBN). RESULTS: Of the 1777 TNBC patients receiving NACT, 54 achieved pathologic complete response (pCR) and 755 had residual disease. Most patients were overweight with stage II disease (78%), grade 3 tumors (53%), and RDBN score 3 (42%). Compared to baseline, tumor size (30 vs. 15 mm
P <
0.0001) and Ki67 levels (63% vs. 48%
P <
2.2e - 16) generally decreased after NACT. Although only 5% of samples increased in size, Ki67 levels often remained unchanged (75%) or increased (0.9%) after treatment, respectively. However, 34% of patients discontinued treatment. Patients showing no changes in Ki67% had more unfavorable OS (P <
0.0001) and DSS (P = 0.00032), with significantly lower 5-year survival probabilities (OS: 66%
DSS: 78%) than those with decreased Ki67% (OS: 87%
DSS: 89%). All patients reaching pCR were alive 5 years after diagnosis. However, only the RDBN score was an independent predictor of survival in the multivariable analyses. CONCLUSION: Ki67 often remained unchanged in TNBC patients treated with neoadjuvant chemotherapy, resulting in adverse clinical outcomes. These findings highlight the need for individualized treatment regimens and dynamic monitoring of TNBC patients with high Ki67 post-NACT.