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

Not Applicable

Not yet recruiting

• Conditions: Breast Cancer Early Stage Breast Cancer (Stage 1-3)
• Interventions: Drug: Endocrine Therapy of Physician's Choice

• Registration Number: NCT07153757
• Lead Sponsor: Fudan University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-08-26
• Status Verified: 2025-09
• Study Start: 2025-09-01
• Study First Submitted QC: 2025-09-03
• Last Update Submitted: 2025-09-03
• Study First Posted: 2025-09-04
• Last Update Posted: 2025-09-04
• Primary Completion: 2033-09-01
• Study Completion: 2033-09-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 2934

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
5 years of standard endocrine therapy	Endocrine Therapy of Physician's Choice	The control group receives 5 years of standard endocrine therapy: Premenopausal patients: Tamoxifen (10 mg, orally, twice daily, for 5 years) or Toremifene (60 mg, orally, once daily, for 5 years); Postmenopausal patients: Letrozole (2.5 mg, orally, once daily, for 5 years) or Anastrozole (1 mg, orally, once daily, for 5 years) or Exemestane (25 mg, orally, once daily, for 5 years); A sequential regimen of 2-3 years of Tamoxifen or Toremifene followed by 3-2 years of Letrozole, Anastrozole, or Exemestane is acceptable. Ovarian function suppression is permitted for premenopausal patients. CDK4/6 inhibitors are not allowed during the treatment course
2-3 years of de-escalated endocrine therapy	Endocrine Therapy of Physician's Choice	The experimental group receives 2-3 years of endocrine therapy: Premenopausal patients: Tamoxifen (10 mg, orally, twice daily, for 2-3 years) or Toremifene (60 mg, orally, once daily, for 2-3 years); Postmenopausal patients: Letrozole (2.5 mg, orally, once daily, for 2-3 years) or Anastrozole (1 mg, orally, once daily, for 2-3 years) or Exemestane (25 mg, orally, once daily, for 2-3 years). Ovarian function suppression is permitted for premenopausal patients. CDK4/6 inhibitors are not allowed during the treatment course.

Primary Outcome Measures

Name	Time	Method
5-year disease-free survival in the per-protocol population	5 year	The proportion of patients in a clinical trial who remained free of disease recurrence, secondary primary cancers, and death from the disease for five years following treatment initiation, calculated specifically among those who completed the study intervention as predefined in the trial protocol(i.e., without major deviations such as incomplete treatment, use of prohibited therapies, or significant protocol violations).

Secondary Outcome Measures

Name	Time	Method
Quality of Life score in the per-protocol population	5 year	The quality of life of patients was assessed using the EORTC QLQ-C30 questionnaire before, during, and after treatment.
safety	5 year	the evaluation of the adverse effects and potential risks of an investigational medical product (e.g., drug, device, or intervention) on participants throughout the study.
5-year disease-free survival in the Full Analysis Set	5 year	The proportion of patients in a clinical trial who remained free of disease recurrence, secondary primary cancers, and death from the disease for five years after randomization or initiation of treatment, analyzed within the Full Analysis Set (FAS) population-which includes all subjects randomized (or initially assigned to a treatment group) following the intention-to-treat (ITT) principle, regardless of whether they fully received, discontinued, or deviated from the protocol.
5-year invasive breast cancer-free survival in the per-protocol population	5 year	The proportion of participants in a clinical trial who, after receiving the full intended course of treatment without major protocol deviations, remained free of invasive ipsilateral or contralateral breast cancer recurrence, distant metastatic invasive breast cancer, and death from any cause for a period of five years from the start of treatment or randomization.
Overall survival in the per-protocol population	5 year	The length of time from randomization or initiation of treatment until death from any cause, measured specifically among participants who completed the study intervention without major protocol deviations, such as insufficient treatment exposure, use of prohibited therapies, or significant violations of inclusion/exclusion criteria.

Trial Locations

Locations (1)

270 Dongan Road, Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, China