The prognostic value of tumor quadrant in breast cancer patients achieving pathologic complete response: a retrospective cohort study from the Sir Run Run Shaw Hospital database

Background: A clinically significant proportion of patients who achieve pathologic complete response (pCR) still experience unfavorable long-term outcomes. Traditional clinical trials often oversimplify the binary assessment of pCR, whereas real-world observational data are needed to capture the heterogeneity of post-pCR outcomes and to refine risk stratification. This retrospective cohort study utilizes real-world data from the Sir Run Run Shaw Hospital database to analyze factors associated with adverse outcomes in pCR patients.

Methods: This retrospective study included 293 patients from Sir Run Run Shaw Hospital (2005–2024) who achieved pCR (ypT0/is ypN0) after neoadjuvant therapy (NAT). This study included patients with a diagnosis of unilateral breast cancer, female sex, and without histopathological evidence of malignant cells in both the breast and axillary lymph nodes post-surgery. Baseline characteristics were compared between patients with and without subsequent disease progression. Univariable Cox proportional hazards regression was performed to identify factors associated with event-free survival (EFS). Kaplan-Meier curves with log-rank tests were used to visualize EFS differences among tumor quadrants, the only variable with statistical significance in univariable analysis. Five-year and 10-year EFS rates were estimated by the Kaplan-Meier method. Analyses were conducted using R software.

Results: This study included 1,773 patients who had received NAT and overall pCR rate was 16.5% (n=293), with subtype-specific rates of 33.5% human epidermal growth factor receptor 2 (HER2)-positive breast cancer, 13.3% triple-negative breast cancer (TNBC), and 6.1% (luminal). Among pCR patients, 16 patients (5.4%) experienced disease progression (5 recurrences, 10 metastases, and 8 deaths). With a median follow-up of 41 months, progression-free survival was shorter in patients with progression events compared to those without progression events (24 vs. 41 months, P<0.001). In baseline characteristic comparisons between pCR patients with and without subsequent disease progression, Ki-67 was the only variable that differed significantly between the two groups (P<0.05), which did not reach statistical significance in univariate Cox analysis. Tumor quadrant was the only variable that demonstrated a statistically significant association with EFS in univariable Cox analysis (overall P=0.01 by likelihood ratio test; log-rank P=0.06). Patients with tumors in the outer upper quadrant had zero progression events, whereas those in the outer lower and inner upper quadrants exhibited the lowest survival rates (5-year EFS: 83.1% and 88.6%; 10-year EFS: 83.1% and 70.9%, respectively).

Conclusions: In this cohort of breast cancer patients achieving pCR after NAT, tumor quadrant was significantly associated with EFS, with the outer upper quadrant showing the most favorable outcomes. Although Ki-67 differed between progression groups at baseline, it did not retain prognostic significance in time-to-event analysis. These findings suggest that tumor location may be associated with post-pCR outcomes, warranting validation in larger cohorts.