Pathological Complete Response and Safety of Neoadjuvant Pembrolizumab-Based Chemoimmunotherapy in Triple-Negative and Hormone Receptor-Low Breast Cancer: A Real-World Cohort Study.

Abstract

Background: Neoadjuvant pembrolizumab-based chemoimmunotherapy is standard of care for early-stage triple-negative breast cancer (TNBC). Real-world data remain limited outside trial populations, particularly in the Middle East, and hormone receptor (HR)-low tumors (ER/PR 1-10%) are undercharacterised in this setting.

Methods: We conducted a retrospective cohort study of 149 patients with non-metastatic TNBC or HR-low breast cancer at King Hussein Cancer Center, Jordan (April 2021-September 2024). Primary endpoint was pCR (ypT0/Tis ypN0), analysed across all 149 treatment-initiated patients with the 7 who did not undergo surgery classified as non-pCR; Firth penalised logistic regression identified factors independently associated with pCR. Safety was assessed in all 149.

Results: The overall pCR rate was 59.1% (88/149). On Firth penalised multivariable logistic regression, three variables were independently associated with pCR: grade 3 histology (aOR 4.44, 95% CI 1.61-13.66, p = 0.004), pathogenic germline mutation (aOR 3.19, 95% CI 1.26-9.11, p = 0.014), and age younger than 40 years (aOR 2.82, 95% CI 1.20-7.10, p = 0.017). HR-low tumors (n = 15) achieved 66.7% pCR, comparable to HR-negative disease (58.2%). Immune-related adverse events occurred in 44 patients (29.5% of 149); grade ≥3 events in 9 (20.5% of irAE patients; 6.0% of the cohort); permanent immunotherapy discontinuation for treatment-limiting toxicity in 6 (13.6% of irAE patients; 4.0% of the cohort). Hospitalization occurred in 33.6%, predominantly due to febrile neutropenia. At a median follow-up of 27.3 months, 137 of 149 patients (91.9%) were alive and 136 (91.3%) were recurrence-free; all 13 recurrences were distant. Among surgical patients, disease-free survival was 96.6% in the pCR group versus 85.2% with residual disease (log-rank p = 0.011).

Conclusion: In this real-world Middle Eastern cohort, pembrolizumab-based chemoimmunotherapy achieved pCR rates consistent with pivotal trial data. Grade 3 histology, pathogenic germline mutation, and age younger than 40 years were independently associated with pCR; the HR-low findings are exploratory. These results support prospective biomarker-driven trials in early TNBC across underrepresented populations.