Lymphovascular Invasion in SOUND-Eligible Breast Cancer: Implications for Occult Axillary Nodal Metastasis

The SOUND randomized controlled trial demonstrated that omitting sentinel lymph node biopsy (SLNB) is noninferior to performing SLNB in early-stage breast cancer. Lymphovascular invasion (LVI), however, is an adverse pathologic feature associated with axillary nodal metastasis. In this study, we evaluated the association of LVI with occult axillary nodal metastasis in early-stage, SOUND-eligible breast cancer.

We retrospectively reviewed patients with cT1N0 breast cancer from 2011 to 2025 who underwent upfront breast-conserving surgery and lymph node surgery who met SOUND trial eligibility criteria. Clinicopathologic variables were collected, and Pearson's chi-square test, unpaired t-test, and logistic regression were used to analyze the cohort.

We identified 364 cT1N0 breast tumors, of which 63 (17.3%) were LVI-present. The overall nodal upstaging rate (pN+) was 11.3%. However, pN+ among LVI-present patients was 33.3% compared with 6.6% among LVI-absent patients (OR 7.03; 95%CI 3.51, 14.05; p < 0.001). Only 1 case (0.3%) had extensive nodal disease (pN2) in which LVI was present. On multivariate analysis for predictors of LVI-present, premenopausal (OR 4.23, 95%CI 2.31, 7.76; p < 0.001) was significantly associated with LVI-present, and well differentiated was significantly associated with LVI-absent (OR 0.060, 95%CI 0.010, 0.47; p = 0.0071). On multivariate analysis for predictors of pN+, only LVI-present (OR 6.47, 95%CI 3.14, 13.34 p < 0.001) was significantly associated with pN+.

Pathologic-confirmed LVI was present in one-third of patients with SOUND-eligible breast cancer with axillary nodal metastasis. LVI-present was independently predictive of axillary nodal metastasis and may have implications for decision-making regarding SLNB-omission.