Contemporary therapy for small node-negative triple-negative breast cancer: a retrospective cohort study

Introduction Multi-agent neoadjuvant therapy (NAT) with immune checkpoint blockade is standard treatment for Stage II–III triple-negative breast cancer (TNBC), though its role in smaller node-negative tumors remains unclear. Methods We performed a retrospective multi-institutional cohort study evaluating demographics, treatment patterns, and outcomes in a contemporary “small TNBC” population (n = 215) comprising Stage I (n = 154) and Stage II, T < 3 cm TNBC (n = 61). Results Within the small TNBC cohort, Stage II, < 3 cm tumors demonstrated higher rates of grade 3 histology (93.4% vs 74.7%, p = 0.0013), NAT (85.2% vs 61.0%, p = 0.0006), adjuvant pembrolizumab (56.8% vs 24.7%, adjusted p = 0.0024), and neoadjuvant KEYNOTE-522 (75.0% vs 45.7%, adjusted p = 0.0052) compared with Stage I disease. Despite these treatment differences, recurrence and mortality rates were similar between groups. Among NAT-treated patients with small TNBC (n = 146), the pathologic complete response (pCR) rate was 51.3% (75/146), without significant difference between Stage I and Stage II, < 3 cm tumors (51.1% vs 51.9%, p = 0.92). There were no significant differences in regimen-specific pCR rates or event-free survival (EFS) when comparing NAT between Stage I and Stage II, < 3 cm tumors, or comparing NAT vs. no NAT for the small TNBC cohort. Conclusions Stage I and Stage II, < 3 cm TNBC demonstrated overlapping clinicopathologic features, pCR rates, and short-term survival outcomes despite substantially different treatment approaches. These findings suggest that current stage-based treatment distinctions may not fully capture the clinical behavior of small TNBC and support further prospective evaluation of risk-adapted and size-based treatment frameworks to better individualize NAT selection in this understudied population.