Can we omit surgical axillary staging in early-stage invasive lobular carcinoma?: Results from a large multicenter retrospective cohort study.

Abstract

588 Background: The SOUND, INSEMA and BOOG 2013-08 randomized trials demonstrated that, in selected patients with clinically node-negative (cN0) early-stage breast cancer, omission of sentinel lymph node biopsy (SLNB) results in non-inferior disease-free and invasive disease-free survival. However, invasive lobular carcinoma (ILC) was under-represented in these three studies, and the safety of this approach in ILC remains uncertain due to concerns about a potentially higher axillary nodal burden and risk of undertreatment. We evaluated the axillary nodal burden in ILC patients who met the trials eligibility criteria. Methods: This retrospective multicenter study included patients with cT1-2 cN0 ILC, undergoing upfront surgery between 2012 and 2025 across three high-volume Italian institutions. All patients underwent preoperative axillary ultrasound (US), with needle biopsy performed for US-suspicious lymph nodes. Uni- and multivariable logistic regression analyses identified factors associated with advanced nodal disease (pN2/3). Results: A total of 1886 patients (median age 65 years) were included. The median radiologic tumor size was 16 mm (IQR 11-23). Most patients underwent SLNB (84%), while the remaining were treated with axillary dissection. The overall rate of pN2/3 disease was 2.5% (48/1886). On univariable analyses, a palpable mass on physical exam (OR 3.59; p < 0.001), the presence of US-suspicious axillary nodes (OR 8.19; p < 0.001), tumor size > 2 cm (OR 2.96; p = 0.002), multicentric disease (OR 4.5; p < 0.0001), high tumor grade (OR 2.15; p = 0.03), the presence of lymphovascular invasion (LVI) (OR 3.25; p = 0.001) and HER2 positivity (OR 3.81; p = 0.022) were significantly associated with pN2/3 disease. On multivariable analysis, tumor size > 3 cm (p = 0.003), the presence of US-suspicious axillary nodes (OR 6.29; p = 0.002), the presence of LVI (OR 3.65; p = 0.006), multicentric distribution (OR 5.19; p < 0.0001), and HER2 positivity (OR 3.86; p = 0.041) were independently associated with pN2/3 disease. Conclusions: In this large real-world cohort of SOUND/INSEMA eligible patients with ILC, the rate of pN2/3 disease was 2.5%, higher than that reported in the aforementioned trials. Omission of axillary surgical staging in patients harboring high risk features may result in understaging, with potential implications for adjuvant treatment decisions and oncologic outcomes. Meticolous selection is critical to identify patients who are not at risk of potential undertreatment.