Prognostic impact of extensive nodal involvement in small-sized (T1) breast cancer: a population-based and propensity score-matched analysis of the SEER database.

BACKGROUND

The prognostic significance of extensive nodal involvement (N2-3) in patients with small-sized (T1) breast cancer remains to be fully elucidated. This study aimed to compare the clinicopathological characteristics and survival outcomes between T1N0-1M0 and T1N2-3M0 breast cancer.

METHODS

Patients diagnosed with T1 breast cancer between 2010 and 2012 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Clinicopathological features were compared using Chi-squared tests and t-tests. Overall survival (OS) and breast cancer-specific survival (BCSS) were assessed using Kaplan-Meier analysis and Cox regression. Propensity score matching (PSM) was performed to minimize confounding effects. Competing risk analysis using the Fine-Gray model was also conducted to compare the cumulative incidence of breast cancer-specific death, accounting for death from other causes as a competing event.

RESULTS

Of 60,318 eligible patients with T1M0 breast cancer, 2.9% (n=1,772) had T1N2-3M0 disease. Compared to the T1N0-1M0 cohort, these patients were younger, had higher T substages, less frequent hormone receptor positivity, higher human epidermal growth factor receptor 2 (HER2) positivity and tumor grade, and received more aggressive surgical and systemic therapy (all P<0.001). Before matching, T1N2-3M0 status was associated with significantly worse 5-year OS [86.9% vs. 96.4%; hazard ratio (HR) =3.50] and BCSS (89.7% vs. 98.7%; HR =7.79). In multivariable analysis, advanced nodal status remained the strongest independent risk factor for both OS [adjusted hazard ratio (aHR) =2.83] and BCSS (aHR =3.86). After 1:1 PSM (n=3,512), survival disparities persisted, though attenuated (OS: HR =2.23; BCSS: HR =2.82). Competing risk analysis accounting for death from other causes confirmed a significantly higher cumulative incidence of breast cancer-specific death in the T1N2-3M0 group (Gray's test: χ2 =56.47, P<0.001). At 60 months, the cumulative incidence was 11.95% [95% confidence interval (CI): 10.29-13.73%] in the T1N2-3M0 group vs. 4.09% (95% CI: 3.14-5.22%) in the T1N0-1M0 group, with no significant difference in death from other causes (P=0.40). In the matched multivariable model, T1N2-3M0 status retained its strong independent prognostic value for OS (aHR =2.36) and BCSS (aHR =2.92), along with higher tumor grade and negative hormone receptor status.

CONCLUSIONS

Even within T1 breast cancer, extensive nodal involvement (N2-3) defines a distinct subgroup with more aggressive tumor biology and significantly poorer survival, independent of other clinicopathological factors. This underscores the critical need for comprehensive nodal staging and potentially more intensive treatment strategies for T1N2-3 patients.