Predictors of Pathologic Complete Response and Its Prognostic Value in Early Breast Cancer: A Real-World Cohort Study

Pathologic complete response (pCR) after neoadjuvant systemic therapy (NAST) is a key prognostic marker in early breast cancer (EBC), particularly in triple-negative (TNBC) and HER2-positive subtypes. However, real-world data on predictors of pCR and their impact on survival remain limited.

We retrospectively analyzed 200 patients with stage II-III EBC treated with NAST at a single institution (2015-2023). Clinicopathologic variables and treatment characteristics were evaluated for association with pCR (ypT0/is ypN0), and histological regression was additionally assessed using the Miller-Payne scoring system. Multivariable logistic regression identified independent predictors. Disease-free survival (DFS) and overall survival (OS) were estimated using Kaplan-Meier methods.

Overall, 36.0% achieved pCR, with the highest rates in HER2-positive (65%) and TNBC (56%) subtypes. Independent predictors of pCR included HER2 positivity (OR 4.21, 95% CI 1.83-9.67, p < 0.001), high Ki-67 > 47.5% (OR 3.62, 95% CI 1.68-7.80, p = 0.001), ER < 10% (OR 2.77, 95% CI 1.18-6.50, p = 0.019), and radiologic complete response (OR 10.03, 95% CI 2.91-34.60, p < 0.001). At a median follow-up of 75 months, compared with non-pCR, patients achieving pCR had a significantly lower risk of recurrence (HR 0.16, 95% CI 0.04-0.70, p = 0.014) with 5-year DFS rates of 91.5% vs. 72.8%. For OS, pCR patients showed a lower risk of death (HR 0.33, 95% CI 0.07-1.49, p = 0.150), corresponding to 5-year OS of 92.2% vs. 87.0%, although this difference was not statistically significant.

HER2 positivity, high Ki-67, low ER expression, and radiologic complete response are independent predictors of pCR. Achieving pCR strongly correlates with improved DFS but not OS, likely due to limited sample size and event number. These findings reinforce pCR as a surrogate endpoint in TNBC and HER2-positive disease and highlight the need for post-neoadjuvant escalation in non-pCR patients.