Which CDK4/6 drug is easiest to tolerate in early breast cancer?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Age ≥18 years with clinical stage II-III breast cancer at the time of signing informed consent. 2. Post-operative pathological confirmation of invasive breast cancer that is hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-), as confirmed by the research center's pathology department: * ER positive and/or PR positive defined as ≥10% of tumor cells showing positive nuclear staining. * HER2 negative defined as immunohistochemistry (IHC) 0 or 1+, or negative by in situ hybridization (ISH). 3. Pathologically confirmed unilateral primary invasive breast cancer, with the date of breast cancer diagnosis on the pathology report no more than 18 months before randomization. For patients with multicentric or multifocal tumors, all pathologically examined lesions must meet the pathological requirements in criterion . 4. For patients who received adjuvant chemotherapy: the last chemotherapy dose must be at least 21 days before randomization. 5. For patients who received adjuvant radiotherapy: the last radiotherapy session must be at least 14 days before randomization. 6. The last non-endocrine treatment (including surgery, radiotherapy, chemotherapy) must be within 90 days before randomization. 7. Has undergone curative surgical resection with tumor-free margins on pathological examination, and meets one of the following high-risk categories: * Pathologically confirmed tumor involvement in ≥4 ipsilateral axillary lymph nodes; OR ② Pathologically confirmed tumor involvement in 1-3 ipsilateral axillary lymph nodes AND at least one of the following: a. Pathological primary invasive tumor size ≥5 cm; b. Primary tumor histological grade 3 (G3); c. Ki-67 ≥20%; d. Known genetic test indicating high risk of recurrence. 8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 9. No evidence of recurrence or metastatic disease after surgery. 10. Adequate organ and bone marrow function, meeting the following criteria: * White blood cell (WBC) count ≥3,000/mm³ (3.0 × 10⁹/L) (without G-CSF within 14 days); * Absolute neutrophil count (ANC) ≥1,500/mm³ (1.5 × 10⁹/L) (without G-CSF within 14 days); * Platelet count (PLT) ≥100,000/mm³ (100 × 10⁹/L) (without corrective treatment within 7 days); * Hemoglobin (Hb) ≥9 g/dL (90 g/L) (without corrective treatment within 7 days); ⑤ Serum creatinine ≤1.5 × upper limit of normal (ULN) or creatinine clearance ≥60 mL/min (without corrective treatment within 7 days); ⑥ Total bilirubin (TBIL) ≤1.5 × ULN (without corrective treatment within 7 days); ⑦ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN (without corrective treatment within 7 days); ⑧ QTcF ≤470 ms. 11. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days before randomization, and must agree to use acceptable non-hormonal contraception from the signing of informed consent until 7 months after the last dose of dalpiciclib, or 21 days after the last dose of abemaciclib/ribociclib, or 2 months after the last dose of aromatase inhibitor or tamoxifen/toremifene (whichever is longer). 12. All toxicities from prior anti-cancer therapy must have recovered to grade 0-1 (CTCAE version 6.0), except for those explicitly stated in the inclusion/exclusion criteria. 13. Has voluntarily signed the informed consent form, and is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: 1. Pathological diagnosis of HER2-positive breast cancer (HER2-positive defined as immunohistochemistry \[IHC\] 3+ or positive by in situ hybridization \[ISH\]). 2. Local or regional recurrence of breast malignancy. 3. Clinical stage IV (metastatic) breast cancer. 4. Bilateral breast cancer (including contralateral carcinoma in situ). 5. History of any malignancy other than breast cancer within 5 years before randomization, excluding adequately treated cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma of the skin. 6. History of severe pulmonary disease such as interstitial pneumonia. 7. Prior treatment with any CDK4/6 inhibitor, other anti-cancer biologic therapy, targeted therapy, or cancer immunotherapy. 8. Concurrent participation in another clinical trial of anti-cancer therapy (including endocrine therapy or immunotherapy). 9. Major surgical procedure, receipt of any investigational drug, other anti-cancer treatment, or use of immunomodulators within 4 weeks before randomization (excluding chemotherapy, radiotherapy, and endocrine therapy for breast cancer). 10. Known infection with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS); active hepatitis B (HBV DNA ≥500 IU/mL); hepatitis C (positive hepatitis C antibody with HCV-RNA above the lower limit of detection of the assay); or co-infection with hepatitis B and hepatitis C. 11. Any of the following within 6 months before randomization: myocardial infarction, severe/unstable angina pectoris, New York Heart Association (NYHA) class ≥2 heart failure, persistent arrhythmia of grade ≥2 (according to NCI CTCAE version 6.0), atrial fibrillation of any grade, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident (including transient ischemic attack), or pulmonary embolism. 12. Severe infection within 4 weeks before randomization (e.g., requiring intravenous antibiotics, antifungals, or antivirals per clinical practice guidelines), or unexplained fever \>38.5°C during screening or before the first dose. 13. Inability to swallow, intestinal obstruction, or other factors affecting drug administration or absorption. 14. Known hypersensitivity to aromatase inhibitors, tamoxifen-class drugs (e.g., tamoxifen, toremifene), and LHRH agonists; known hypersensitivity to dalpiciclib/abemaciclib/ribociclib or any of their excipients 15. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. 16. Known history of substance abuse (including psychoactive drugs). 17. Women within 1 year postpartum or currently breastfeeding. 18. Presence of any other serious physical or psychiatric condition, or laboratory abnormality that may increase the risk of study participation, interfere with study results, or render the patient unsuitable for the study in the opinion of the investigator.