De-escalation Therapy in Stage I ER-Positive Breast Cancer: A Non-Inferiority Trial

A Prospective, Randomized, Open-label, Non-inferiority, Phase III Study Evaluating the Efficacy and Safety of 2 to 3 Years of Adjuvant Endocrine De-escalation Therapy for ER-positive/HER2-negative Stage I Breast Cancer

This study is a prospective, randomized, open-label, non-inferiority Phase III clinical trial, planning to enroll 2,934 patients, with a 1:1 allocation to either the conventional endocrine therapy group or the de-escalation therapy group. The aim is to evaluate the safety and efficacy of 2-3 years of de-escalated endocrine therapy in patients with T1N0M0 potentially low-risk breast cancer, respectively.

Inclusion Criteria:

• Females aged 18 years or older;

• Postoperative pathological stage I early breast cancer: histologically confirmed invasive carcinoma with a maximum diameter ≤2 cm and node-negative (N0);

• Immunohistochemistry (IHC) shows ER-positive (ER ≥50%), HER2 IHC score of 0, 1+, or 2+ with no amplification confirmed by FISH, and Ki-67 ≤20%;

• Presence of at least one of the following potential low-risk factors:

  1）Tumor size ≤1 cm, 2）21-gene recurrence score <11, 3）Fudan digital pathological subtype classified as SNF1, 4）Age ≥65 years;

• ECOG performance status of 0 or 1;

• Patients with bilateral synchronous invasive lesions are eligible if both lesions are ER-positive, HER2-negative, and meet the tumor size criteria;

• Normal major organ function, meeting the following criteria:

  1. Hematological: HB ≥90 g/L (no transfusion within 14 days), ANC ≥1.5×10⁹/L, PLT ≥100×10⁹/L;
  2. Biochemical: TBIL ≤1.5×ULN, ALT and AST ≤3×ULN, serum Cr ≤1×ULN, and creatinine clearance >50 mL/min (Cockcroft-Gault formula);

• Participants voluntarily enroll, sign informed consent, demonstrate good compliance, and cooperate with follow-up.

Exclusion Criteria:

• Primary tumor size >2 cm in maximum diameter and/or axillary lymph node positivity;
• Prior neoadjuvant therapy, any systemic therapy, or local therapy (except surgery), including chemotherapy, targeted therapy, radiotherapy, or endocrine therapy;
• Prior adjuvant chemotherapy;
• Use of CDK4/6 inhibitors in the adjuvant setting;
• History of other malignancies (except cured basal cell carcinoma or cervical carcinoma in situ);
• Metastasis at any site;
• Pregnancy, lactation, or women of childbearing potential unable to use effective contraception;
• Concurrent participation in other clinical trials;
• Severe cardiac, pulmonary, hepatic, or renal dysfunction; LVEF <50% (by echocardiography); severe cardio-cerebrovascular diseases within 6 months (e.g., unstable angina, chronic heart failure, uncontrolled hypertension >150/90 mmHg, myocardial infarction, or stroke); poorly controlled diabetes; severe hypertension;
• Severe or uncontrolled infections;
• History of drug abuse or psychiatric disorders;
• Patients deemed unsuitable for the study by the investigator.