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

## TL;DR

This study identifies factors that predict a complete cancer response after treatment in early breast cancer patients and shows that achieving this response is linked to better long-term outcomes.

## Contribution

The study provides real-world evidence on predictors of pathologic complete response and its prognostic value in early breast cancer.

## Key findings

- HER2-positive and triple-negative breast cancer patients had the highest rates of pathologic complete response.
- Patients achieving pathologic complete response had significantly lower cancer recurrence rates at five years.
- Radiologic complete response and low estrogen-receptor levels were strong predictors of pathologic complete response.

## Abstract

We studied 200 people with early breast cancer who received treatments before surgery (chemotherapy and, when appropriate, anti-HER2 therapy). Our main goal was to learn which patients are most likely to have no invasive cancer found at surgery—a “pathologic complete response,” which is linked to better outcomes. Overall, 36% reached this outcome, most often in HER2-positive and triple-negative disease. Patients were more likely to clear the cancer if they had HER2-positive tumors, very low estrogen-receptor levels, a high tumor growth index, and a complete response on imaging before surgery. Those who cleared the cancer at surgery had a much lower chance of the cancer returning at five years (about 92% vs. 73% remained cancer-free). These results from routine practice can help doctors identify patients who may benefit from treatment escalation when cancer remains after surgery.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.