eligibility_summary
Inclusion: adults (≥18) with consent, histologic invasive breast cancer stage II–IIIA (≥2 cm and/or cN1–2), HER2 IHC3+, ER/PR status known, PS 0–1, LVEF ≥50%, eligible for neoadjuvant, adequate marrow, hepatic (≤2.5×ULN, Gilbert ok), renal (CrCl >50). Exclusion: pregnancy/breastfeeding, other malignancy (unless non-systemic >5y ago), noncompliance, strong CYP3A4/2C8 meds, chronic liver disease, IBD/resection, MRI contraindication, cT4/cN3 or cT0.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Single-center phase 1b neoadjuvant study in stage II–IIIA HER2+ breast cancer testing chemotherapy-free HER2 blockade: tucatinib (oral small-molecule HER2-selective TKI), trastuzumab (anti-HER2 IgG1 mAb binding domain IV, inhibits signaling and mediates ADCC), and pertuzumab (anti-HER2 mAb binding domain II, blocks HER2 dimerization). In HR+ disease, concurrent endocrine therapy (aromatase inhibitor, LHRH agonist if premenopausal) is given. Targets/pathways: HER2/ERBB2 on tumor cells, inhibition of HER2 phosphorylation and HER2–HER3/EGFR dimerization, downstream PI3K/AKT and MAPK signaling, immune effector ADCC via NK cells, suppression of estrogen signaling (HR+). Responders by DCE-MRI continue chemo-free, non-responders switch to paclitaxel/carboplatin plus trastuzumab/pertuzumab (standard).