Risk of pN2/3 Understaging in Sentinel Node-Positive ER+/HER2-Breast Cancer: A Composite Clinicopathologic Score for Safe RxPONDER and MonarchE Application

Abstract

Background Adjuvant treatment decisions in ER+/HER2- breast cancer depend on accurate distinction between pN1 and pN2/3 disease. As sentinel lymph node biopsy (SLNB) increasingly replaces axillary lymph node dissection (ALND), patients with apparent pN1 disease may be understaged. We evaluated preoperative imaging and developed a composite risk score to identify patients for whom completion ALND might be omitted. Methods We retrospectively analyzed 160 ER+/HER2- patients with 1-3 positive sentinel nodes who underwent completion ALND after upfront surgery. Four imaging modalities were assessed for pN2/3 (>= 4 positive nodes). A five-item composite score (SLN >= 2, lymphovascular invasion, tumor >= 2 cm, Ki-67 >= 20%, multifocality; range 0-5) underwent bootstrap validation and decision curve analysis (DCA). Results All four preoperative imaging modalities failed to predict pN2/3 under-staging (NPV 80-86%; all p >= 0.885). Overall, 17.5% harbored true pN2/3 on completion ALND. Low-risk patients (score <= 1; 32% of cohort) had a pN2/3 rate of only 3.9% (NPV 96.1%; sensitivity 92.9%) versus 23.9% in high-risk patients (p = 0.0015). DCA showed net benefit over a treat-all strategy across clinically relevant thresholds, corresponding to similar to 14 fewer unnecessary ALNDs per 100 patients. Conclusions Preoperative imaging showed limited sensitivity for pN2/3 under-staging and should not alone guide omission of completion ALND. A five-item composite score identified a low-risk subgroup (NPV 96.1%) in whom completion ALND might be omitted without compromising monarchE or RxPONDER decisions; prospective external validation is required before routine adoption.