E2: Differential Prognostic Value of Residual Nodal Burden in Breast Cancer Subtypes

Residual Cancer Burden (RCB) index is highly prognostic in patients with breast cancer (BC) treated with neoadjuvant chemotherapy (NAC). However, RCB does not account for subtype or the precise impact of residual nodal burden (RNB). We aimed to compare the effect of nodal status after NAC on survival among BC subtypes.

Methods: Adult women with stage 1-3 BC diagnosed from 2004-2018 in the National Cancer Database who received NAC followed by surgery within 8 months were included. Axillary dissection was not specifically used as an inclusion criteria. RNB, defined as ypN+, was compared between four subtypes: triple negative breast cancer (TNBC), ER+/HER2+, ER+/HER2-, and ER-/HER2+ patients. RNB was also evaluated as a predictor of mortality with multivariable logistic regression. Kaplan-Meier analyses were performed to compare overall survival, stratified by BC subtypes and RNB.

Results: 69,383 patients were included: 32,880 TNBC, 5,276 ER+/HER2+, 21,216 ER+/HER2-, and 10,011 ER-/HER2+. The majority of patients in each group presented with stage 2 disease (61.2% in TNBC, 57.3% in ER+/HER2+, 55.5% in ER+/HER2-, and 57.2% in ER-/HER2+, p< 0.001). Nodal pathologic complete response was lowest in ER+/HER2- patients at 16.6%, compared to 39.7% of TNBC, 36.6% of ER+/HER2-, and 51.2% of ER-/HER2+ patients (p < 0.001). After adjusting for sociodemographic factors, comorbidities, tumor characteristics, and facility attributes, ypN+ was a predictor of mortality for all BC subtypes and had the strongest predictive effect for TNBC and the least predictive effect for ER+/HER2- patients: for TNBC, ypN1 odds ratio (OR) 2.11 (95% confidence interval [CI95] 1.96-2.27), ypN2 OR 6.91 (CI95 6.11-7.81), ypN3 OR 15.1 (CI95 12.4-18.3); for ER+/HER2+, ypN1 OR 1.29 (CI95 1.02-1.64), ypN2 OR 3.90 (CI95 2.81-5.40), ypN3 OR 4.67 (CI95 2.81-7.77); for ER+/HER2-, ypN1 OR 1.45 (CI95 1.29-1.63), ypN2 OR 2.46 (CI95 2.15-2.82), ypN3 OR 4.51 (CI95 3.83-5.30); and for ER-/HER2+, ypN1 OR 2.01 (CI95 1.71-2.38), ypN2 OR 7.83 (CI95 5.94-10.3), ypN3 OR 10.9 (CI95 7.42-15.9). Comparing overall survival, patients with ypN1 TNBC do worse than those with ypN2 ER+/HER2-, and patients with ypN2 and ypN3 TNBC do significantly worse than those with ypN3 ER+/HER2- (Figure, p< 0.001).

Conclusions: Residual nodal burden has a significantly different impact on survival by breast cancer subtypes, which is not currently captured by the RCB index. This study highlights the poor survival among TNBC patients with high residual nodal burden, and points to the pressing need for improved systemic therapy options for these patients.