Low axillary nodal metastasis rates in selected HER2-positive and triple-negative breast cancer patients: toward de-escalation of sentinel lymph node biopsy

Background: The necessity of sentinel lymph node biopsy (SLNB) is being reconsidered in patients with early breast cancer (BC) who have clinically node-negative disease. However, most de-escalation trials have excluded aggressive subtypes, such as human epidermal growth factor receptor 2 (HER2)-positive BC and triple-negative BC (TNBC), leaving limited data to guide the omission of axillary surgery in these populations. Patients and methods: This multicenter retrospective cohort study included 1,571 patients from four academic institutions who were diagnosed with early-stage HER2-positive BC or TNBC, who had clinically node-negative status on preoperative ultrasonography, and underwent upfront breast-conserving surgery (BCS) with axillary surgery between January 2010 and December 2023. We evaluated rates of pathologic nodal metastasis (pN+) to identify subgroups in which SLNB omission may be feasible. Results: Among 1571 BC patients, 429 (27.3%) had hormone receptor (HR)+HER2+, 359 (22.9%) had HR−HER2+, and 783 (49.8%) had TNBC. Overall, 163 patients (10.4%) had pN+ disease. Independent predictors of pN+ status included suspicious axillary findings on breast magnetic resonance imaging (MRI) (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.38–3.75), larger tumor size (>1.5 cm: OR, 1.99; 95% CI, 1.26–3.15), and lymphovascular invasion (LVI) (OR, 4.86; 95% CI, 3.20–7.36). In a low-risk group ( n = 689 [43.9%]) defined by the absence of suspicious axillary findings on MRI and tumors ≤ 1.5 cm, the pN+ rate was 5.1%, with subtype-specific rates of 7.0% (HR+HER2+), 6.4% (HR−HER2 +), and 3.2% (TNBC). Among the low-risk group, the pN+ rate was 3.2% in those without LVI in the surgical specimen, whereas the pN+ rate was 24.2% in those with LVI. Conclusion: Among ultrasonography-based, clinically node-negative patients with HER2-positive BC or TNBC undergoing upfront BCS, axillary nodal involvement was uncommon when suspicious axillary findings on MRI were absent and tumor size was ≤ 1.5 cm. The pN+ rate was particularly low in patients without LVI in the surgical specimen. While a low axillary nodal burden was identified in selected patients with aggressive subtypes, prospective validation is required before considering the omission of SLNB in clinical practice.