Abstract PD12-06: Axillary nodal upstaging in T1N0 invasive lobular carcinoma: evaluating applicability of SOUND trial results

Abstract Background: Among stage 1, clinically node-negative (cN0), hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer patients with a negative preoperative axillary ultrasound (AxUS), the omission of sentinel lymph node biopsy (SLNB) has been demonstrated to be noninferior to upfront axillary surgery. However, the applicability of this approach to invasive lobular carcinoma (ILC) remains uncertain due to the unreliability of AxUS in ILC and perceived higher risk of nodal upstaging. We sought to evaluate the rate and predictors of axillary nodal upstaging in a cohort of patients with ILC who met SOUND trial criteria. Methods: We retrospectively identified all patients diagnosed with ILC who underwent preoperative axillary ultrasound and upfront surgery including SLNB between 2009 and 2024. cT1, cN0 patients with normal preoperative AxUS were defined as SOUND-eligible (JAMA Oncol 2023). Patients who underwent neoadjuvant systemic therapy (NAST) were excluded. Clinicopathologic characteristics and nodal burden were examined. Both macro- and micrometastasis were included as pathologic nodal metastasis. Descriptive statistics and logistic regression analysis was performed using software R 4.4.2. Results: From an overall cohort of 1059 patients with cT1-3, cN0-2 ILC without NAST who underwent preoperative AxUS and upfront surgery including SLNB, 662 (62.5%) met SOUND trial selection criteria (cT1, cN0 ILC with normal preoperative AxUS). The median age was 60 years (IQR 51-68), median pathologic tumor size was 1.3 cm (IQR 0.9-2.0), and the majority of tumors were classic-type (549, 82.9%), HR+/HER2- (639, 96.5%), and grade 2 (587, 89%). Nodal metastases (pN+) were identified in 116 (17.5%) cases: 24 (3.6%) were pN1mic, 77 (11.6%) pN1, 8 (1.2%) pN2, and 7 (1.0%) pN3. On univariate analysis, histologic grade 3 (OR 3.21, 95% CI 1.01-10.4, p=0.046), lymphovascular invasion (LVI)(OR 6.88, 95% CI 3.51-13.7, p<0.001), and premenopausal status (OR 1.58, 95% CI 1.93-2.41, p=0.033) were significantly associated with pN+ disease. On multivariate analysis, LVI (OR 6.24, 95% CI 3.14-12.6, p<0.001) was the only independently associated factor with the finding of pN+ disease. Due to only a few upstaging events to pN2-3 (n=15), UVA and MVA could not be performed in this subgroup. LVI was present in 5 (33.3%) of the 15 cases with pN2-3 upstaging. Conclusions: In this cohort of ILC who met SOUND eligibility criteria, 17.5% of patients were node positive, and only 2.2% of patients had extensive nodal upstaging (pN2-3). High-risk features, such as presence of LVI, premenopausal status, and high grade, may be useful for decision making for omission of SLNB in stage 1 ILC patients. Citation Format: T. Amburn, A. Mamtani, J. J. Chen, V. Sevilimedu, S. Shen, K. Jhaveri, M. Morrow. Axillary nodal upstaging in T1N0 invasive lobular carcinoma: evaluating applicability of SOUND trial results [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PD12-06.