Clinical significance of extranodal extension in mastectomy patients with limited sentinel lymph node macrometastases: a retrospective cohort study

Abstract

The clinical significance of extranodal extension (ENE) in patients with one to two macrometastatic sentinel lymph nodes (SLNs) remains controversial in the era of axillary de-escalation. This study evaluated the association between SLN ENE and axillary nodal burden in early breast cancer, specifically addressing the mastectomy population. This retrospective cohort study included early-stage breast cancer patients with one to two macrometastatic SLNs who underwent SLN biopsy followed by axillary lymph node dissection (ALND). Continuous variables were summarized as median (interquartile range) and compared using non-parametric tests. Categorical variables were analyzed using chi-square or Fisher’s exact tests. Logistic regression identified factors associated with SLN ENE and predictors of non-SLN metastasis. Among 191 patients (all mastectomy), 53 (27.7%) had ENE at the SLN. Non-SLN metastasis occurred in 58.5% of patients with ENE compared with 31.2% of patients without ENE (OR 3.11, 95% CI 1.62–5.99; p < 0.001). ENE-positive patients had significantly higher nodal burden than ENE-negative patients (median [IQR]: 1 [0–2.5] vs. 0 [0–1]; p < 0.001). Post-ALND ENE was more frequent in the ENE-positive group (22.6% vs. 5.8%; p < 0.001). No significant difference in non-SLN metastasis was observed between ENE size groups (50.0% vs. 68.0%; OR 2.13, 95% CI 0.75–6.08; p = 0.265), despite a trend toward higher nodal burden in the ENE > 2 mm group ( p = 0.071). ENE independently predicted non-SLN metastasis (aOR 2.94, 95% CI 1.50–5.76; p = 0.002). ENE at the SLN independently predicted non-SLN metastasis in a selected cohort of mastectomy patients with one to two macrometastatic sentinel lymph nodes undergoing completion ALND. No statistically significant association was observed between ENE size and either non-SLN metastasis ( p = 0.265) or axillary nodal burden ( p = 0.071), although the subgroup analysis may have been underpowered to detect moderate differences. These findings support the utility of ENE as a marker of residual axillary disease burden in this specific patient population; however, further validation in larger cohorts is warranted, and the results should not be directly generalized to breast-conserving surgery populations or contemporary axillary de-escalation cohorts.