Fovinaciclib Plus Aromatase Inhibitors and Dual HER2 Blockade in a Response-Adapted Neoadjuvant Strategy for HR-Positive/HER2-Positive Early Breast Cancer

Exclusion Criteria

• •Bilateral breast cancer, inflammatory breast cancer, or occult breast cancer. History of uncontrolled seizures or central nervous system disease. History of other malignancies within the past 5 years. Pregnant or breastfeeding women. Known severe hypersensitivity to any component of the study drugs. Severe comorbidities, including uncontrolled hypertension (e.g., systolic blood pressure \>180 mmHg or diastolic blood pressure \>100 mmHg), uncontrolled diabetes mellitus, or active infection. Patients with adequately controlled hypertension may be enrolled.
• •Clinically uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage or medical intervention within 2 weeks prior to first dosing.
• •Myocardial infarction within 6 months prior to first dosing; uncontrolled arrhythmia (QTc ≥470 ms, calculated using Fridericia's formula); New York Heart Association (NYHA) class III-IV heart failure; LVEF \<50%; or clinically significant pleural effusion, pericardial effusion, or ascites requiring intervention.
• •Dysphagia, active gastrointestinal disease, history of major gastrointestinal surgery, malabsorption syndrome, or any condition that may affect absorption of study drugs.
• •Active hepatitis B infection \[HBsAg-positive with detectable HBV-DNA\], active hepatitis C infection \[HCV antibody-positive with detectable HCV-RNA\], positive syphilis screening (except confirmed inactive infection), known HIV infection, or positive HIV screening result.
• •Receipt of major surgery, radiotherapy, tumor immunotherapy, monoclonal antibody-based antitumor therapy, or other systemic antitumor therapies considered by the investigator to interfere with study treatment efficacy within 28 days prior to first dosing.
• •Planned or previous organ transplantation or bone marrow transplantation. Known history of psychiatric substance abuse or drug addiction. Any other condition that, in the investigator's judgment, would make the subject unsuitable for participation in the study.