RecurIndex Guided Avoidance of Regional Nodal Irradiation for Node Positive Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to validate whether clinically low-risk, and RecurIndex high-risk N1 patients receiving regional lymph node radiotherapy can further improve clinical outcomes.

Official Title
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RecurIndex Guided Avoidance of Regional Nodal Irradiation for Node Positive Breast Cancer

Conditions
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Breast Cancer, Radiation

Intervention / Treatment
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* Radiation: regional nodal irradiation
* Radiation: WBI
* Radiation: chestwall XRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old, ≤ 70 years old. Eastern Cooperative Oncology Group (ECOG) ≤ 2. Postoperative pathology is clearly diagnosed as invasive breast cancer. Meet the clinical definition of low risk: ①Axillary lymph node micrometastasis (N1mic) or ②N1 patients who meet the following conditions at the same time, a）Age ≥ 40 years old, b）Vascular tumor thrombus (LVI) negative or allow few positive LVI (excluding extensive or massive LVI), c）Three subtypes are allowed (Lumina A, Lumina B/HER2 negative, Lumina B/HER2 positive) , namely ER positive (ER ≥ 1%), HER2 negative (HER2 expression negative or + by IHC, or 2+ but negative by FISH) or ER positive (ER ≥ 1%), HER2 positive (3+ by IHC, or 2+ but positive by FISH). Postoperative pathological diagnosis of axillary lymph node status is any of the following: a. Sentinel lymph node biopsy or axillary lymph node dissection for micrometastasis (N1mic), b. Sentinel lymph node biopsy for 1-2 lymph node macrometastasis (N1sln), c. Sentinel lymph node biopsy + axillary lymph node dissection or simple axillary lymph node dissection for 1-3 lymph node metastasis (N1). The primary tumor and breast undergo breast-conserving surgery or total resection ± breast reconstruction (autologous/prosthetic). There must be adequate systemic examination (such as chest X-ray, B-ultrasound, CT, etc.) within 3 months before randomization of radiotherapy to confirm that there is no distant metastasis. No contralateral breast cancer must be confirmed by molybdenum target and/or MRI within 12 months before randomization of radiotherapy. At least 4 courses of adjuvant chemotherapy with anthracycline or taxane should be completed after surgery. Radiotherapy must be performed sequentially after the completion of adjuvant chemotherapy, starting no later than 8 weeks after the end of chemotherapy. The patient must have sufficient primary fresh frozen specimens or post-paraffin tissue sections for RecurIndex testing. No previous history of malignant tumors, except for basal cell carcinoma of the skin. Signed an informed consent form. Exclusion Criteria: Postoperative radiotherapy was confirmed as T3-4, N0, N2-3, M1 lesion staging before enrollment. Receive any new adjuvant therapy before surgery, including chemotherapy, endocrine therapy, targeted therapy or radiation therapy. Patients who underwent total mastectomy and only sentinel lymph node biopsy. Have a history of contralateral breast cancer. History of chest radiotherapy. combined with severe heart, lung, liver, kidney, hematopoietic, neurological diseases, and mental illness. History of autoimmune diseases such as scleroderma or active lupus erythematosus. pregnant and lactating patients. Unable or unwilling to sign an informed consent form.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (Clinical low-risk, RecurIndex high-risk)<br>Regional nodal irradiation (RNI) was given along with whole breast irradiation (WBI) or Chest wall irradiation (CWI) for breast-conserving patients and total mastectomy patients, respectively. | Radiation: regional nodal irradiation<br>* external-beam radiotherapy (XRT)<br>Radiation: WBI<br>* Whole Breast Irradiation<br>Radiation: chestwall XRT<br>* chestwall irradiation<br>|
| Active Comparator: Arm II (Clinical low-risk, RecurIndex high-risk)<br>No Regional nodal irradiation (RNI) , whole breast irradiation (WBI) for breast-conserving patients and No Chest wall irradiation (CWI) for total mastectomy patients. | Radiation: WBI<br>* Whole Breast Irradiation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive disease-free survival (IDFS) | defined as the time between randomization and either local recur, distant metastases or death occurred | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Any first recurrence (AFR) | defined as any recurrence of ipsilateral chest, breast, regional lymph node recurrence, or distant metastases by Imaging or pathology | 5 years | 
| Local-regional recurrence free survival (LRFS) | defined as time between randomization and the time of any recurrence of ipsilateral chest, breast, regional lymph node recurrence, distant metastases, or death occurred | 5 years | 
| Distant metastasis free survival (DMFS) | defined as time between randomization and the time of distant metastases, or death occurred | 5 years | 
| Recurrence free survival (RFS) | defined as time between randomization and the time of any recurrence of ipsilateral chest, breast, regional lymph node recurrence, distant metastases, or death occurred | 5 years | 
| Overall Survival (OS) | defined as time between randomization and the time of death occurred | 5 years | 
| Disease free survival (DFS) | defined as time between randomization and the time of disease recur or death occur | 5 years | 
| Beast cancer specific mortality (BCSM) | defined as time between randomization and the time of death occur specific due to breast cancer | 5 years | 
| Patient life quality measurement | At the screening period and after the end of radiotherapy, each group of patients was enrolled in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Cancer-30 (C30) | 5 years | 
| Patient life quality measurement | At the screening period and after the end of radiotherapy, each group of patients was enrolled in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Breast-23 (BR23) | 5 years |