Predictors of Residual Nodal Disease After Positive Sentinel Lymph Node Biopsy: A Retrospective Cohort Study of Axillary De-escalation in Breast Cancer

Abstract

Background: The management of the axilla following a positive sentinel lymph node biopsy (SLNB) in breast cancer remains a nuanced clinical challenge. A significant proportion of these patients will have no additional nodal disease identified on completion axillary lymph node dissection (ALND)—a phenomenon colloquially referred to in some institutions as the "white axilla" (i.e., no residual nodal disease). This phenomenon questions the universal application of ALND, a procedure associated with considerable morbidity. This study aims to quantify the incidence of no residual nodal disease after positive SLNB and to identify the clinicopathological factors predictive of additional nodal metastases to refine surgical decision-making.

Methods: A single-center, retrospective cohort study was conducted on patients with invasive breast cancer and a positive SLNB who underwent completion ALND at Rotherham Foundation Trust, UK, between 2010 and 2023. Clinicopathological variables including tumor size, grade, receptor status, lymphovascular invasion (LVI), and extracapsular extension (ECE) were analyzed. The predictive performance of the Memorial Sloan Kettering (MSK) nomogram was also evaluated. Multivariable logistic regression was performed, with two separate models for clinicopathological variables and nomogram scores to avoid collinearity. The primary dependent outcome variable for multivariable logistic regression was the presence versus absence of residual nodal metastasis on completion axillary lymph node dissection.

Results: Among 160 eligible patients (after excluding 17 patients due to incomplete histopathology records, prior ipsilateral axillary surgery, or presentation with cN+ disease), 96 (60.0%) exhibited no further nodal involvement. This group was characterized by significantly lower Nottingham Prognostic Index (NPI) scores (mean 4.8 vs. 5.06, p=0.042), smaller median primary tumor size (33.7 mm vs. 39.1 mm, p=0.038), and a lower incidence of ECE (31.3% vs. 53.1%, p=0.006). Multivariate logistic regression identified tumor size >35 mm (adjusted OR 2.11, 95% CI 1.08-4.12, p=0.028), presence of ECE (adjusted OR 2.63, 95% CI 1.36-5.09, p=0.004), and HER2-negative status (adjusted OR 3.87, 95% CI 1.23-12.21, p=0.021) as independent predictors of non-sentinel node metastasis. The MSK nomogram demonstrated good discriminatory ability (AUC 0.81, 95% CI 0.74-0.88) when analyzed as a continuous variable in a separate model.

Conclusion: The high proportion of patients without residual nodal disease in this cohort suggests that completion ALND may be unnecessary for many patients with a positive SLNB. The identified predictive factors may help guide a more selective, personalized approach to axillary management. These findings should be interpreted with awareness of the institutional practice pattern during this era, recognizing that evaluating Z0011 adherence was not a goal of this study. Prospective validation is warranted.