eligibility_summary
Women 18–80, ECOG 0–1, untreated, non‑metastatic HER2+ breast cancer (T1cN1 or T2 N0–1), HER2 3+ in ≥80% cells, ER ≤10%, PR <1%, tumor ≥10 mm and SUVmax ≥2.5. Provide FFPE tissue, LVEF ≥55%, contraception/negative pregnancy test if WOCBP. Exclude metastatic, T4, N2–3 or inflammatory, prior systemic/anti‑HER2/endocrine or ipsilateral RT, bilateral disease, prior excisional/ALND/SLNB, significant comorbidity, organ or cardiac dysfunction, active infection, investigational therapy.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Interventions: PHESGO (fixed‑dose subcutaneous pertuzumab + trastuzumab, monoclonal antibodies) as neoadjuvant therapy, adjuvant options include PHESGO alone (if pCR) or T‑DM1 (trastuzumab emtansine, HER2‑directed antibody–drug conjugate delivering the microtubule inhibitor DM1) or investigator’s choice chemotherapy + PHESGO. Mechanisms: Trastuzumab binds HER2 domain IV to inhibit HER2 signaling and mediate ADCC via Fcγ receptors, pertuzumab binds domain II to block HER2 dimerization (notably HER2–HER3), enhancing dual blockade and suppressing downstream PI3K/AKT and MAPK pathways, T‑DM1 internalizes and releases DM1, disrupting microtubules in HER2+ cells. Targets: HER2‑overexpressing breast cancer cells, HER2/ERBB2 receptor and HER2–HER3 dimers, downstream growth/survival signaling, immune effector (NK cell) ADCC. Biomarker focus: HER2 IHC 3+ (≥80% cells), ER‑low/PR‑, and early FDG‑PET metabolic response.