The Presence of Extensive Lymphovascular Invasion (LVI) is Associated with Higher Risk of Recurrence in Curatively Treated Breast Cancer Patients

Abstract

Lymphovascular invasion (LVI) is a pathological feature seen in breast cancer that may be an important step in cancer metastasis. Multiple datasets have demonstrated a correlation between LVI and local-regional recurrence (LRR). Whether the extent of LVI is an incremental determinant of LRR risk is unknown. We describe clinical outcomes in women with invasive breast cancer stratified by: 1) absence of LVI (neg), 2) LVI focal or suspicious (FS-LVI), 3) usual (non-extensive) LVI (LVI) and 4) extensive LVI (E-LVI). Between December 2009 and August 2021, there were 8,837 patients with early-stage breast cancer (T1-2 and N0-2a) were treated with curative intent and were evaluable. Clinical-pathological details were abstracted by retrospective review. The description of LVI was abstracted from pathology reports. Recurrence and survival outcomes were compared based on the extent of LVI. Of the 8837 patients studied, 5584 were neg, 461 had FS-LVI, 2315 had LVI, and 477 had E-LVI. The E-LVI cohort had baseline characteristics suggestive of higher risk such as younger median age, higher proportion of grade 3, more nodal positivity, more mastectomy (67% vs 48%), and higher use of chemotherapy compared to LVI. The cumulative incidence of LRR and DM was highest in the E-LVI group. Using LVI as the reference, the presence of E-LVI, age, tumor size, ER status, grade, mastectomy, and close/positive margins were independent variables for LRR on Cox multivariable regression (Table 1). To assess the effect with an alternate statistical method, we created propensity matched cohorts (matched for age, size, receptors, grade, surgery type, margins and chemotherapy/RT use); a statistical difference in OS was noted between groups with LVI vs E-LVI (HR 1.44 (CI 1.06-1.96, p = 0.018), but not in LRR (HR 1.31 (CI 0.87-1.97, p = 0.2) or DM (HR 1.16 (CI 0.88-1.53, p = 0.3). Our work suggests that patients with E-LVI are at a higher risk for LRR compared to patients with usual LVI, despite maximal standard of care treatment. This is important because E-LVI can be determined from breast specimens, and may help define indications for RNI/PMRT when nodal information is not available.