Novel Prognostic Stratification and Therapeutic Implications in T1N0M0 Breast Cancer: Insights from a Multi-Center Chinese Cohort

Background: Early-stage breast cancer (T1N0M0 BC) generally has a favorable prognosis, but relapse risks persist over time. The role of adjuvant systemic treatments (AST) for tumors ≤ 10 mm remains debated. Given the limited availability of robust prospective data, retrospective studies play a crucial role in guiding clinical decision-making. Methods: This multicenter retrospective study included 1,733 invasive T1N0M0 breast cancer patients treated at two Chinese centers (1998–2018). Patients with neoadjuvant chemotherapy or unknown estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2) status were excluded. Primary endpoint was disease-free survival (DFS); secondary endpoints included distant recurrence-free survival (DRFS), breast cancer-specific survival (BCSS), and overall survival (OS). Survival outcomes across four molecular subtypes (ER, PR, HER2-defined) were analyzed using Kaplan–Meier and Cox models. Tumor size thresholds for AST benefit were determined via maximally selected rank statistics. Results: This study evaluated 1,733 T1N0M0 breast cancer patients, with HR+/HER2 − as the most common subtype (56.9%), followed by HR+/HER2+ (12.6%), HR-/HER2+ (10.8%), and triple-negative (19.7%). Molecular subtypes showed significant prognostic stratification (10-year DFS: 84.0% for HR+/HER2- vs 73.4% for HR-/HER2+, P  < 0.001). AST demonstrated significant overall benefit (DFS HR = 0.33, 95% CI: 0.24–0.45, P  < 0.001), with consistent improvements in DRFS, BCSS, and OS (all P  < 0.01). Subtype-specific thresholds were identified: no AST benefit for HR+/HER2 − tumors < 10 mm ( P  = 0.33 for endocrine therapy); significant DFS improvement for HER2 + tumors ≥ 8 mm receiving trastuzumab (HR = 0.37, 95% CI: 0.14–0.77, P  = 0.018); and for triple-negative tumors ≥ 9 mm (HR = 0.38, 95% CI: 0.21–0.74, P  = 0.002). Conclusion: This study highlights the prognostic heterogeneity of T1N0M0 breast cancer and identifies high-risk subgroups that benefit from AST. Integrating molecular and clinicopathologic features supports a more personalized approach to early-stage breast cancer treatment.