Abstract
ABSTRACT
This prospective single‐arm study evaluated neoadjuvant disitamab vedotin plus penpulimab in Stage II–III HER2‐low breast cancer (immunohistochemistry 1+ or 2+, fluorescence in situ hybridization‐negative), a population lacking targeted neoadjuvant options. Twenty patients received the combination every 3 weeks for six cycles before surgery. In the intention‐to‐treat population, the pathologic complete response (pCR) was 20.0% (four out of 20; 95% CI, 5.7–43.7%), and the objective response rate (ORR) was 45.0% (nine out of 20; 95% CI, 23.1–68.5%). Among 16 patients who completed protocol‐defined treatment and surgery, pCR was 25.0% (four out of 16; 95% CI, 7.3–52.4%), ORR was 56.3% (nine out of 16; 95% CI, 29.9–80.2%), and 31.3% achieved residual cancer burden Class 0–1. Grade ≥3 adverse events occurred in 25.0%; no treatment‐related deaths occurred. pCR‐associated tumors had a pretreatment immune‐active microenvironment enriched in inflammatory proteins, transcripts, and tumor‐infiltrating lymphocytes, whereas nonresponders displayed a higher M2/M1 macrophage ratio. An exploratory baseline score combining CCL19 and the M2/M1 ratio showed pCR/non‐pCR separation (AUC = 0.8889) but attenuated on internal validation (LOOCV AUC = 0.6667, optimism‐corrected bootstrap AUC = 0.8375). This combination showed preliminary antitumor activity with manageable safety; however, given the small sample size and wide confidence intervals, these findings preclude definitive conclusions about efficacy and warrant validation in larger randomized controlled trials.