Chemotherapy Omission in HR-positive/HER2-negative Breast Cancer With Lymph Node Negative Disease Receiving Adjuvant Endocrine Therapy and CDK4/6 Inhibitor

This is a prospective, randomized, open-label, multicenter phase III study to explore chemotherapy omission in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer with lymph node negative disease receiving adjuvant endocrine therapy and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor.

In this study, patient eligible will be randomized into either standard endocrine therapy plus CDK4/6 inhibitor without chemotherapy or standard endocrine therapy plus CDK4/6 inhibitor following 4 cycles of TC (docetaxel + cyclophosphamide) adjuvant chemotherapy.The safety and efficacy of each group will be assessed through invasive disease free survival (iDFS), disease-free survival (DFS), distant disease free survival (DDFS), overall survival (OS) and adverse effects (AE) as graded by Common Terminology Criteria for Adverse Events (CTCAE) 5.0 and patient reported outcome (PRO).

Inclusion criteria

• Females and males aged 18-70 years;
• ECOG performance status 0-1;
• Early-stage breast cancer, with postoperative pathology confirming invasive carcinoma, HR-positive and HER2-negative (In this study, HR-positive is defined as: ER-positive by IHC with >10% tumor cells staining positive; HER2-negative defined as HER2 0-1+ by IHC or HER2++ with negative FISH result, without amplification);
• Postoperative pathological stage pT2N0M0 and:

Histological grade 3, or Histological grade 2 with Ki67 ≥ 20% or high-risk multigene assay results;

• No prior neoadjuvant therapy received;
• Good postoperative recovery, with randomization occurring no more than 8 weeks after surgery;
• Normal function of major organs, meeting the following criteria:

Hematological tests must meet: HB ≥90 g/L (no transfusion within 14 days); ANC ≥1.5×10⁹/L; PLT ≥100×10⁹/L; Biochemical tests must meet: TBIL ≤1.5×ULN (upper limit of normal); ALT and AST ≤3×ULN; serum Cr ≤1.5×ULN;

• Contraception required for male participants and women of childbearing potential during treatment;
• Participants voluntarily enroll in the study, sign informed consent, demonstrate good compliance, and cooperate with follow-up.

Exclusion criteria

• Bilateral breast cancer or carcinoma in situ (DCIS/LCIS);
• Metastasis at any site;
• Clinical or imaging suspicion of malignancy in the contralateral breast requiring biopsy (unless ruled out);
• Prior neoadjuvant therapy, including chemotherapy, radiotherapy, or endocrine therapy;
• Use of tamoxifen, raloxifene, or aromatase inhibitors (AIs) for breast cancer risk reduction ("chemoprevention") and/or osteoporosis treatment within the past 2 years;
• History of other malignancies within the past 5 years (except basal cell carcinoma of the skin or carcinoma in situ of the cervix), including contralateral breast cancer;
• Concurrent participation in another clinical trial;
• Severe systemic diseases and/or uncontrolled infections that preclude study participation;
• Severe cardiovascular or cerebrovascular events within 6 months before randomization (e.g., unstable angina, chronic heart failure, uncontrolled hypertension >150/90 mmHg, myocardial infarction, or stroke);
• Known hypersensitivity to the study drugs;
• Men and women of childbearing potential unwilling to use contraception during treatment and for 8 weeks after treatment completion;
• Pregnant or lactating women;
• Positive pregnancy test before study drug administration (for women of childbearing potential);
• Psychiatric disorders, cognitive impairment, or inability to comprehend the trial protocol, adverse effects, or comply with study procedures and follow-up (requires systematic evaluation before enrollment);
• Individuals lacking personal freedom or legal capacity for independent civil conduct.