Is It Time to Redefine Clinical Nodal Staging for Breast Cancer?

The current American Joint Committee on Cancer (AJCC) staging system defines cN1 by node mobility rather than number, while pathologic staging stratifies by node count. Whether cN1 patients with four or more suspicious nodes on pretreatment imaging differ in pathologic stage and survival outcomes from those with fewer nodes is unclear.

Patients with biopsy-proven cN1 or cN2a breast cancer diagnosed in 2018-2023 who received neoadjuvant chemotherapy (NAC) at a single institution were identified. Pretreatment imaging was reviewed and cases categorized as cN1a (1-3 mobile nodes), cN1b (≥ 4 mobile nodes), or cN2a (matted nodes). Clinicopathologic characteristics were compared using χ² and Kruskal-Wallis tests. DFS and OS were estimated with Kaplan-Meier curves and multivariable Cox regression.

Among 618 cases, 390 (63.1%) were cN1a, 166 (26.9%) cN1b, and 62 (10.0%) cN2a. Pathologic complete response (pCR) rates did not differ across groups (29.5%, 28.9%, 35.5%; P = 0.598). Among patients with residual nodal disease, mean positive nodes were 2.8, 4.6, and 5.5 in cN1a, cN1b, and cN2a (P < 0.001), respectively. Pathologic nodal stage was ypN2 or higher in 12.8%, 24.1%, and 29.0% (P = 0.001), and cN1b was independently associated with upstaging on multivariable analysis (OR 1.958, 95% CI 1.184-3.237, P = 0.009). At median follow-up of 41.4 months, 3-year DFS (88.0%, 89.0%, 80.6%; P = 0.949) and OS (91.6%, 92.3%, 91.6%; P = 0.947) did not differ across groups.

In cN1 breast cancer, imaging-defined nodal burden ≥ 4 nodes independently predicts upstaging and greater residual nodal burden after NAC, aligning pathologically with cN2a disease. Imaging-based subcategorization of cN1 disease may have implications for staging, surgical planning, and trial eligibility.