Ki-67 expression and rates of pathologic complete response in T1cN0M0 triple-negative breast cancer: a national cancer database analysis.

PURPOSE: Treatment sequencing for T1cN0M0 triple-negative breast cancer (TNBC) remains controversial because neoadjuvant chemotherapy (NACT) has not demonstrated improved overall survival (OS) compared to adjuvant chemotherapy (ACT). Using pathologic complete response (pCR) as an early, positive prognostic indicator, this study evaluates how Ki-67 expression levels impact pCR rates in T1cN0M0 TNBC to identify patients who benefit most from upfront chemotherapy. METHODS: The National Cancer Database (NCDB) was queried (2018-2022) for female patients aged ≥ 18 with T1N0M0 TNBC undergoing chemotherapy and surgery. Patients were grouped into NACT or ACT cohorts and balanced using inverse probability of treatment weighting (IPTW). Cox multivariate analysis evaluated OS predictors, while logistic regression identified factors associated with pCR. A ROC curve was created for Ki-67 expression in the setting of pCR and the maximum Youden index established a threshold value. RESULTS: An analysis of 8,831 patients from the NCDB found no significant difference in OS between NACT and ACT, but multivariate analysis revealed lymphovascular invasion (LVI), invasive lobular subtype (ILC), and mixed invasive lobular/ductal subtype were associated with worse OS. In the NACT group, there was a 3.59 h for worse OS in non-pCR patients compared to those achieving pCR. Ki-67 expression was strongly associated with pCR rates, with Ki-67 ≥ 45.8% yielding a 45.3% pCR rate compared to 21.8% for Ki-67 < 45.8%. CONCLUSION: Although OS did not differ between NACT and ACT in T1cN0M0 TNBC, achieving pCR after NACT significantly improved survival. A Ki-67 threshold of ≥ 45.8% predicted higher pCR rates and can guide patient selection for upfront chemotherapy. CLINICAL TRIAL NUMBER: Not applicable.