Neoadjuvant Endocrine Therapy Combined With Chemotherapy in ER-positive, HER2-negative Stage I-III Breast Cancer

NCT07801898 | Not Yet Recruiting Phase 2

• 1 other identifier: YX2023-203（F1）
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this investigator-initiated, open-label, phase II clinical trial is to evaluate the efficacy and safety of neoadjuvant chemotherapy combined with endocrine therapy in patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, Ki67 \> 20% invasive breast cancer. The main questions it aims to answer are: What is the objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 criteria at the completion of neoadjuvant treatment? What are the changes in Ki-67 proliferation index, pathological tumor response, pathological complete response (pCR) rate, disease-free survival (DFS), and safety profile? Participants will receive standard anthracycline- and taxane-based chemotherapy with letrozole. The chemotherapy regimen was either six cycles of docetaxel, epirubicin, and cyclophosphamide (TEC) every 3 weeks or four cycles of epirubicin plus cyclophosphamide followed by four cycles of a taxane (EC→T). The investigator could replace docetaxel or paclitaxel with nanoparticle albumin-bound paclitaxel (nab-paclitaxel), depending on the patient's clinical features and treatment tolerance. Patients took letrozole 2.5 mg orally once daily throughout neoadjuvant systemic therapy. Premenopausal patients also received ovarian function suppression with leuprorelin acetate (3.75 mg) subcutaneously every 28 days, from the start of neoadjuvant treatment until definitive surgery. A safety assessment will be conducted for each treatment cycle in the patient. During the neoadjuvant therapy phase, tumor assessment will be performed at least after 4 cycles and preoperatively; postoperatively, assessments will be conducted every 3 months using imaging modalities to evaluate the tumor status until disease progression, death, or completion of 3 years postoperatively occurs. Following surgery, all patients will receive adjuvant therapy selected by the investigator based on their individual clinical condition.

Conditions

Invasive Breast Cancer (Stage I-III)

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR defined as the proportion of patients whose best radiological response during neoadjuvant treatment was complete response (CR) or partial response (PR) according to RECIST version 1.1.

  At the end of Cycle 4 and prior to surgery (each cycle is 21 days)

Secondary Outcomes (5)

• pCR

  At time of definitive surgery (each cycle is 21 days)

• Pathological Response

  At time of definitive surgery (each cycle is 21 days)

• Paired change in Ki67 between biopsy and surgery

  From baseline biopsy to definitive surgery (each cycle is 21 days)

• Disease-Free Survival (DFS)

  From definitive surgery to 36 months post-surgery (each cycle is 21 days)

• Treatment-related adverse events (TRAEs)

  From first dose to 30 days after last dose

Study Arms (1)

Experimental Drug Group

EXPERIMENTAL

Drug: NaCET: For chemotherapy, the TEC or EC-T regimen is selected; for endocrine therapy, letrozole is administered; for premenopausal patients, an LHRH agonist-goserelin or leuprolide

Interventions

NaCET: For chemotherapy, the TEC or EC-T regimen is selected; for endocrine therapy, letrozole is administered; for premenopausal patients, an LHRH agonist-goserelin or leuprolide DRUG

Patients received NaCET consisting of standard anthracycline- and taxane-based chemotherapy administered concurrently with letrozole. The preferred chemotherapy regimen was TEC, comprising docetaxel, epirubicin, and cyclophosphamide, administered every 3 weeks for six cycles. A sequential EC→T regimen, consisting of four cycles of epirubicin plus cyclophosphamide followed by four cycles of a taxane, was also permitted. At the investigator's discretion, nab-paclitaxel could be substituted for docetaxel or paclitaxel according to individual patient characteristics, treatment tolerance, and clinical considerations. Letrozole was administered orally at 2.5 mg once daily throughout the entire neoadjuvant chemotherapy period. Premenopausal patients additionally received ovarian function suppression with leuprorelin 3.75 mg subcutaneously every 28 days, beginning at initiation of neoadjuvant treatment and continuing throughout the preoperative treatment period.

Experimental Drug Group

Eligibility Criteria

• Age: 18 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Eligible patients were aged ≥18 years
• Histologically confirmed estrogen ER-positive, HER2-negative breast cancer with a Ki67 proliferation index \>20%.
• ER-positivity was defined as nuclear staining in ≥1% of tumor cells by immunohistochemistry (IHC). HER2-negative disease was defined as an IHC score of 0 or 1+, or an IHC score of 2+ with negative fluorescence in situ hybridization(FISH).
• Patients were required to have stage I-III operable or locally advanced breast cancer according to the eighth edition of the American Joint Committee on Cancer staging system.
• Patients with clinically node-negative disease (cN0) were additionally required to have high-risk clinical features, including a primary tumor classified as cT2 or higher and/or a markedly elevated Ki67 proliferation index.

You may not qualify if:

• Previous chemotherapy or endocrine therapy for breast cancer;
• Pregnancy or lactation;
• Severe or uncontrolled infection;
• Clinically significant cardiovascular disease, including New York Heart Association class III or IV heart failure, unstable angina, or myocardial infarction within 6 months before enrollment;
• Left ventricular ejection fraction \<50%;
• A history of organ transplantation requiring ongoing immunosuppressive therapy;
• Known human immunodeficiency virus infection;
• A concurrent or previous malignancy that could interfere with the assessment of study outcomes;
• Psychiatric, cognitive, or other medical conditions that could impair treatment adherence or compliance with study procedures.

Sponsors & Collaborators

• The Second Hospital of Anhui Medical University: lead

Study Sites (1)

The Second Hospital of Anhui Medical University

Hefei, Anhui, 230601, China

Location

MeSH Terms

Interventions

Drug Therapy; Leuprolide

Intervention Hierarchy (Ancestors)

Therapeutics; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Central Study Contacts

Yanyan Hong

CONTACT

（86）0551-63869536; aydefyhyy@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Chief Physician

Study Record Dates

• First Submitted: August 26, 2026
• First Posted: September 3, 2026
• Study Start: September 30, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): March 30, 2029
• Last Updated: September 3, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)