Does the Number of Positive Nodes in pN1 Premenopausal HR

The RxPONDER trial showed premenopausal patients with pT1-2 N1 hormone receptor-positive (HR+)/HER2- breast cancer benefit from chemotherapy regardless of 21-gene recurrence score (RS), but it did not analyze whether the number of positive lymph nodes (+LNs) was correlative of outcomes. Our study sought to evaluate whether the number of +LNs predicted chemotherapy benefit in pN1 premenopausal women with a low RS. Using the National Cancer Database, we identified females younger than 50 years with HR+/HER2- invasive breast cancer, stratified by RS (<25 and > 25) and number of +LNs. We analyzed clinicopathologic features, adjuvant therapies received, and overall survival (OS). Within the cohort of 12,017 patients, 86% had a RS ≤25, whereas 77% had 1 +LN, 18% had 2 +LNs, and only 5% had three +LNs. Of patients with RS ≤25, 57% had endocrine therapy alone and 38% had combination chemoendocrine therapy. Chemotherapy omission was associated with worse unadjusted OS in the overall cohort and in the subgroup with only 1 +LN (both P < 0.001). Factors associated with worse adjusted OS were Black race (hazard ratio 1.91), intermediate/high tumor grade (hazard ratios 1.93 and 3.75), T2 tumors (hazard ratio 1.59), having 2 or 3 +LNs (hazard ratios 1.53 and 2.17), the use of endocrine therapy alone (hazard ratio 1.64), and increasing RS (hazard ratio 1.08; all P < 0.05). Chemotherapy was omitted in more than half of the patients younger than 50 years with RS ≤25 during the study period, and omission was associated with worse OS in every LN category. These findings confirm the benefit of chemotherapy even in patients with limited nodal disease.