Evaluating the Response-Guided Therapy With Neoadjuvant Endocrine Therapy to Optimize Adjuvant Treatment in Premenopausal HR+/HER2- Breast Cancer (JCOG2402, Youg HOPE) (Young HOPE)

A Randomized Phase III Study of Response-Guided Therapy Following Neoadjuvant Endocrine Therapy to Optimize Adjuvant Treatment in Premenopausal HR+/HER2- Breast Cancer (JCOG2402, Young HOPE)

Young HOPE/JCOG2402 is a multicenter, randomized phase III study designed to evaluate response-guided therapy following neoadjuvant endocrine therapy to optimize adjuvant treatment in premenopausal HR+/HER2- Breast Cancer.

Premenopausal women with intermediate-risk HR-positive/HER2-negative breast cancer derive benefit from the addition of chemotherapy to endocrine therapy. However, previous studies have demonstrated that patients who achieve an endocrine response (Ki-67 ≤10%) following neoadjuvant endocrine therapy have excellent outcomes without chemotherapy, irrespective of menopausal status. These findings suggest that endocrine therapy response may serve as a predictive biomarker to identify premenopausal patients who can safely omit chemotherapy.

The primary objective of this study is to evaluate the non-inferiority of an ET response-guided treatment strategy compared with standard surgery followed by adjuvant therapy. The study aims to increase the proportion of patients who can be treated with endocrine therapy alone by omitting chemotherapy in those with highly endocrine-sensitive disease.

Eligible patients are randomized 1:1 to upfront surgery or neoadjuvant endocrine therapy with an aromatase inhibitor and ovarian function suppression. The primary endpoint is EFS. Secondary endpoints include overall survival, relapse-free survival, distant recurrrence-free survival, HR-QOL, the rate of endocrine therapy alone in adjuvant therapy, ET response rate in an Arm B, the rate of non-menopause and safety. A total of 950 patients will be enrolled. Randomization is stratified by cN0 vs cN1, HG1 or 2 vs 3, and institution.

The JCOG2402 trial addresses an unmet need in adjuvant therapy of premenopausal HR-positive, HER2-negative breast cancer with intermediate risk and may contribute to the establishment of a new treatment strategy.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Adjuvant systemic therapy based on pathological findings; Drug: Adjuvant systemic therapy based on pathological findings and ET response

• Study Type: Interventional
• Enrollment (Estimated): 950
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Makiko Ono, MD; Phone Number: +81333538111; Email: makikono@gmail.com

Study Locations

• Japan
  • Kashiwa, Japan
    • Recruiting
    • National Cancer Center Hospital East
  • Tokyo, Japan
    • Recruiting
    • National Cancer Center Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Women aged 18 years or older
2. ECOG PS 0-1
3. HR-positive/HER2-negative breast cancer
4. ER expression ≥ 10%
5. cN0; HG 1: 3 cm<T≤5 cm, HG 2: 2 cm<T≤5 cm or HG3: 1 cm<T≤5 cm cN1; cT<5 cm and HG 1/HG 2
6. Premenopausal women with spontaneous menses within 12 months
7. No distant metastasis of breast cancer
8. No prior diagnosis of breast cancer.
9. No multiple regions of breast cancer
10. No contralateral breat cancer
11. Adequate organ function

Exclusion Criteria:

1. Presence of active double cancer (synchronous malignancy requiring treatment).
2. Ongoing infectious disease requiring systemic therapy. Fever ≥38.0°C at the time of registration.
3. Women who are pregnant, possibly pregnant, within 28 days postpartum, or breastfeeding; men whose partners intend to become pregnant.
4. Psychiatric illness or symptoms that interfere with daily living and may compromise trial participation.
5. Ongoing systemic administration (oral or IV) of steroids equivalent to ≥10 mg/day of prednisolone or other immunosuppressive agents.
6. Unstable angina (developed or worsened within the past 3 weeks) or myocardial infarction within the past 6 months.
7. Uncontrolled hypertension.
8. Uncontrolled diabetes mellitus despite continuous insulin or oral antidiabetic therapy.
9. Positive for HBs antigen or HCV antibodies (Patients positive for HCV antibodies are not excluded if HCV-RNA is undetectable.)
10. Positive for HIV antibodies (HIV testing is not mandatory.)
11. Presence of interstitial pneumonia, pulmonary fibrosis, or severe emphysema as diagnosed by chest CT.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Upfront surgery (Arm A); Participants in Arm A will undergo breast surgery and adjuvant systemic treatment.	Drug: Adjuvant systemic therapy based on pathological findings; Patients with Oncotype DX recurrence score (RS) ≧16 (pN0) or pN1 are treated with chemotherapy and endocrine therapy with ovarian function suppression (OFS). Adjuvant chemotherapy for pN0 and pN1 is TC and anthracycline-taxane, respectively. Aromatase inhibitor or tamoxifen co-administered with a LHRH agonist for 5 years. The choice of AI is per investigator discretion. The choice of LHRH agonist and dosing schedule is per investigator's discretion. Endocrine treatment beyond 5 years is at the investigator's discretion. Patients with RS ≤ 15 are treated with tamoxifen.
Experimental: Neoadjuvant endocrine therapy (Arm B); Participants in Arm B will receive neoadjuvant endocrine therapy of aromatase inhibitor and OFS for three months, followed by breast surgery.	Drug: Adjuvant systemic therapy based on pathological findings and ET response; If patients with Oncotype DX RS between 16-25 (for pN0 patients) and 0-25 (for pN1 patients) have an ET response (Ki-67 ≤10%), they are treated with endocrine therapy plus OFS without chemotherapy. Patients without an ET response or with high risk (RS ≧26) receive chemotherapy and endocrine therapy with OFS. Patients with RS ≤ 15 (pN0) are treated with tamoxifen. Adjuvant chemotherapy for pN0 and pN1 is TC and anthracycline-taxane, respectively. Aromatase inhibitor or tamoxifen is co-administered with a LHRH agonist for 5 years. The choice of AI is per investigator discretion. The choice of LHRH agonist and dosing schedule is per investigator's discretion. Endocrine treatment beyond 5 years is at the investigator's discretion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event free survival	Time from randomization to the first diagnosis of local invasive recurrence, regional recurrence, distant recurrence, contralateral invasive breast cancer, inoperable progressive disease during neoadjuvant endocrine therapy, second primary invasive non-breast cancer (excluding non-melanoma skin cancer and in situ cervical cancer), or death from any cause	Up to 12 years (5 years of accrual and 7 years of follow-up)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time from randomization to death from any cause	Up to 12 years (5 years of accrual and 7 years of follow-up)
Relapse-free survival	Time from randomization to the first diagnosis of relapse or death from any cause	Up to 12 years (5 years of accrual and 7 years of follow-up)
Distant recurrence-free survival	Time from randomization to the first diagnosis of distant recurrence of breast cancer or death from any cause	Up to 12 years (5 years of accrual and 7 years of follow-up)

Collaborators and Investigators

• Sponsor: Tokyo Women's Medical University
• Collaborators: Japan Clinical Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2026
• Primary Completion (Estimated): January 27, 2038
• Study Completion (Estimated): January 27, 2039

Study Registration Dates

• First Submitted: June 22, 2026
• First Submitted That Met QC Criteria: June 22, 2026
• First Posted (Actual): June 26, 2026

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 22, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Premenopausal women; HR+HER2-; neoadjuvant endocrine therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: JCOG2402; jRCTs031250687 (Registry Identifier: Japan Registry of Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No