ctDNA-Guided De-Escalation of Adjuvant Chemotherapy With Dalpiciclib in HR-Positive/HER2-Negative Breast Cancer

Inclusion criteria

• Female breast cancer patients aged ≥18 years and ≤75 years, either postmenopausal or premenopausal/perimenopausal;
• Pathologically confirmed hormone receptor-positive (HR+), HER2-negative invasive breast cancer:
• ER-positive and/or PR-positive defined as: ≥10% of tumor cells showing positive staining;
• HER2-negative defined as: standard immunohistochemistry (IHC) result of 0/1+; or IHC 2+ with negative in situ hybridization (ISH) (confirmed by the central pathology laboratory);
• At least one evaluable lesion per RECIST 1.1, with clinical staging meeting:
• T1c-2N0M0 with high-risk factors (Grade 3, or Grade 2 with Ki67 ≥20%);
• T3N0M0;
• Any TN+M0;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
• Willing to participate in the study and voluntarily sign informed consent;
• Agree to undergo ctDNA testing during treatment;
• Adequate organ and bone marrow function defined as:
• Absolute neutrophil count (ANC) ≥1,500/mm³ (1.5 × 10⁹/L) (without granulocyte colony-stimulating factor \[G-CSF\] treatment within 14 days);
• Platelet count (PLT) ≥100,000/mm³ (100 × 10⁹/L) (without corrective therapy within 7 days);
• Hemoglobin (Hb) ≥9 g/dL (90 g/L) (without corrective therapy within 7 days);
• Serum creatinine ≤1.5× upper limit of normal (ULN) or creatinine clearance ≥60 mL/min (without corrective therapy within 7 days);
• Total bilirubin (TBIL) ≤1.5×ULN (without corrective therapy within 7 days);
• Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤1.5×ULN (without corrective therapy within 7 days);
• Cardiac function: left ventricular ejection fraction (LVEF) ≥55%; QTc interval corrected by Fridericia's formula (QTcF) \<470 msec on 12-lead ECG;
• Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization and agree to use non-hormonal contraception from informed consent signing until 2 months after the last treatment.

Exclusion criteria

• HER2-positive breast cancer confirmed by current pathological diagnosis;
• Inflammatory breast cancer;
• Stage IV (metastatic) breast cancer;
• Bilateral breast cancer;
• Prior history of breast cancer (including ductal carcinoma in situ or invasive breast cancer);
• Any prior antitumor therapy for the current breast cancer, including systemic therapies (endocrine, chemotherapy, immunotherapy, biological therapy) or local therapies (radiotherapy, vascular embolization, axillary lymph node biopsy);
• Diagnosis of any malignancy within 5 years prior to randomization, except cured cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma of the skin;
• History of severe pulmonary diseases (e.g., interstitial pneumonia);
• HIV infection, acquired immunodeficiency syndrome (AIDS), active hepatitis B (HBV DNA ≥500 IU/mL), hepatitis C (HCV antibody-positive with HCV RNA above the lower limit of detection), or co-infection with HBV and HCV;
• Within 6 months prior to randomization: myocardial infarction, severe/unstable angina, NYHA Class ≥II heart failure, ≥Grade 2 persistent arrhythmia (per NCI CTCAE v5.0), atrial fibrillation of any grade, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident (including transient ischemic attack), or symptomatic pulmonary embolism;
• Severe active infection within 4 weeks prior to randomization (requiring intravenous antibiotics, antifungals, or antivirals) or unexplained fever \>38.5°C during screening/before first dose;
• Known allergy to any component of the study drugs;
• Current participation in another interventional drug clinical study;
• Pregnancy or lactation;
• Refusal to comply with follow-up;
• Other severe physical/mental illnesses or laboratory abnormalities that may increase study risk, interfere with results, or render the patient unsuitable per investigator judgment.