Distant recurrence–free survival in invasive lobular carcinoma (ILC) with isolated tumor cells: Does pN0(i+) behave like node-negative or node-positive disease?

587 Background: ILC is a distinct breast cancer subtype with unique biology and clinical behavior compared with invasive ductal carcinoma. The prognostic significance of isolated tumor cells (ITCs; pN0(i+)) in ILC remains unclear, creating a management gap regarding whether patients with ITCs should be risk-stratified and treated similarly to node-negative (pN0) or node-positive (pN1) disease. Methods: We performed a retrospective analysis of patients with ILC treated at The University of Texas MD Anderson Cancer Center (Protocol PA20-0040). Distant recurrence-free survival (DRFS) was assessed using Kaplan-Meier methods and compared using log-rank testing. Univariate and multivariable Cox proportional hazards models evaluated associations between clinicopathologic and treatment variables and DRFS. The multivariable model included age, pathologic nodal stage, grade, HER2 status, histologic subtype (classical vs non-classical), and receipt of endocrine therapy, chemotherapy, radiation therapy, and definitive surgery. Results: The cohort included 4,217 patients (mean age 56.8 years). Most tumors were classical ILC (89.1%). ITCs were present in 169 patients; comparator groups included pN0 (n=1,799) and pN1 (n=1,040). In univariate analysis, there was no evidence that pN0(i+) were associated with worse DRFS versus pN0 (ITC negative) (HR 0.71, 95% CI 0.45-1.13; p=0.135), whereas pN1 was associated with inferior DRFS versus pN0 (HR 1.85, 95% CI 1.62-2.10; p<0.001). In multivariable analysis, there remained no evidence that pN0(i+) were associated with inferior DRFS versus pN0 (HR 0.661, 95% CI 0.404-1.081; p=0.099), while pN1 was independently associated with worse DRFS versus pN0 (HR 1.922, 95% CI 1.589-2.326; p<0.0001). Conclusions: In this large ILC cohort, pN0(i+) (ITCs) did not confer inferior DRFS compared with pN0, and outcomes were clearly distinct from pN1 disease. These findings support prospective validation and may inform nodal-status-driven risk stratification and treatment de-escalation strategies for pN0(i+) patients with ILC. Key DRFS comparisons (reference = pN0). Comparison Univariate HR (95% CI) Univariate p-value Multivariable HR (95% CI) Multivariable p-value pN0(i+) vs pN0 0.71 (0.45-1.13) 0.135 0.661 (0.404-1.081) 0.099 pN1 vs pN0 1.85 (1.62-2.10) <0.001 1.922 (1.589-2.326) <0.0001