Clinicopathologic and Treatment-Related Determinants of Pathologic Complete Response and Survival Outcomes in Triple-Negative Breast Cancer: A Real-World Cohort Study

Background: Pathological complete response (pCR) following neoadjuvant systemic therapy is an important prognostic indicator in triple-negative breast cancer (TNBC). Nevertheless, identifying clinicopathological characteristics associated with treatment response remains essential. This study aimed to evaluate factors associated with pCR and the relationship between pCR and survival outcomes in patients with TNBC receiving neoadjuvant therapy. Methods: In this retrospective cohort study, 153 patients with stage I–III TNBC who received neoadjuvant systemic therapy followed by surgery between April 2010 and January 2025 were evaluated. Clinicopathological characteristics, including age, menopausal status, body mass index (BMI), histological grade, HER2 status, Ki-67 proliferation index, tumor-infiltrating lymphocytes (TILs), clinical tumor stage, clinical nodal stage, and neoadjuvant treatment regimen were analyzed. Factors associated with pCR were evaluated using basic and expanded multivariable logistic regression models. The basic model included treatment regimen, histological grade, and clinical nodal status, while the expanded model additionally included HER2 immunohistochemical category, Ki-67, and clinical T stage. Complete-case analysis was performed to address missing data. Overall survival (OS) and event-free survival (EFS) were evaluated using the Kaplan–Meier method. Results: The basic multivariable logistic regression model included 143 patients and identified clinical node positivity as independently associated with lower odds of achieving pCR (adjusted OR = 0.285; 95% CI: 0.119–0.682; p = 0.005). Histological grade 3 (adjusted OR = 3.117; p = 0.010) and a pembrolizumab-containing treatment regimen (adjusted OR = 4.194; p = 0.015) were associated with higher odds of achieving pCR; however, the overall test for treatment regimen was not statistically significant (p = 0.112). In the expanded model (n = 133), clinical node positivity remained independently associated with lower odds of achieving pCR (adjusted OR = 0.318; 95% CI: 0.129–0.783; p = 0.013). Although the directions of the associations were maintained for histological grade 3 (p = 0.094) and the pembrolizumab-containing regimen (p = 0.052), neither association reached statistical significance. Tumor-infiltrating lymphocyte (TIL) data were available for only 67 patients, and no statistically significant association between TIL levels and pCR was observed in this subgroup. Patients who achieved pCR had more favorable overall survival (OS) and event-free survival (EFS) outcomes than those with residual disease. Conclusions: Baseline clinical nodal status was consistently associated with pathological complete response (pCR) across different multivariable models in patients with triple-negative breast cancer (TNBC). Findings regarding histological grade and pembrolizumab-containing neoadjuvant treatment regimens should be interpreted with caution, as these associations did not reach statistical significance in the expanded model. The high proportion of missing tumor-infiltrating lymphocyte (TIL) data further limits conclusions regarding this biomarker. Our study provides real-world evidence on neoadjuvant treatment response and survival outcomes and highlights the need for larger prospective cohorts to further investigate the relationships among clinical nodal status, histological grade, the tumor immune microenvironment, and response to immunotherapy.