Postmastecomy Internal Mammary Nodal Irradiation for High-risk Breast Cancer Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the impact of internal mammary nodal irradiation on disease-free survival in high-risk breast cancer patients treated with mastectomy.

Detailed Description
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Eligible patients are randomized into 2 groups: chest wall and supraclavicular nodal +-axillary plus internal mammary nodal irradiation, and chest wall and supraclavicular nodal +-axillary nodal irradiation. The prescription dose is 50 Gy in 25 fractions over 5 weeks or 43.5Gy in 15 fractions over 3 weeks. During and after radiotherapy, the patients are followed and the efficacy and toxicities of radiotherapy are evaluated.

Official Title
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Postmastectomy Prophylactic Internal Mammary Nodal Irradiation for High-risk Patients With Non-metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Radiation: internal mammary nodal irradiation
* Radiation: no internal mammary nodal irradiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group Performance Status Scale 0-2 Histologically confirmed invasive breast cancer Underwent total mastectomy and axillary dissection(10 or more axillary lymph nodes detected) and negative margins Patients who had ≥4 positive axillary lymph nodes; or 1-3positive axillary lymph nodes and T3-4; or 1-3positive axillary lymph nodes and T1-2, and score≥3 based on the following high risk factors: age≤40 years(score 1), primary tumor in the inner quadrant (score 1), 2-3 positive axillary lymph nodes (score 1), positive vascular invasion (score 1), re-staged based on eighth Cancer Staging System staging system(IB-IIA score 1， IIB-IIIA score 2); or ypN+ after neoadjuvant chemotherapy No supraclavicular or internal mammary nodes metastases based on images before system therapy No distant metastases Could tolerate radiotherapy Treated with chemotherapy (anthracycline and/or taxane-based combined chemotherapy, ≥6 cycles) Anticipated to receive endocrine therapy for 5 years if indicated Anticipated to receive anti-HER2 therapy for 1 years if indicated LVEF≥50% based on echocardiogram Willing to follow up Written,informed consent Exclusion Criteria: Simultaneous bilateral breast cancer Sentinel lymph node biopsy only without axillary dissection Had received internal mammary node dissection No imaging assessment of the internal mammary nodal before system therapy One-stage breast reconstruction Severe cardiac insufficiency; myocardial infarction or uncorrected unstable arrhythmia or uncorrected unstable angina in the last 3 months; pericardial disease Had history of chest wall or supraclavicular radiotherapy Had simultaneous or previous secondary malignancies, except for non-malignant melanoma skin cancer, papillary thyroid / follicular carcinoma, cervical carcinoma in situ, contralateral non-invasive breast cancer

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: internal mammary nodal irradiation<br>chest wall and supraclavicular nodal+-axillary plus internal mammary nodal irradiation | Radiation: internal mammary nodal irradiation<br>* chest wall and supraclavicular +-axillary plus internal mammary nodal irradiation (50 Gy in 25 fractions or 43.5Gy in 15 fractions).<br>|
| Active Comparator: no-internal mammary nodal irradiation<br>ipsilateral chest wall and supraclavicular +-axillary nodal irradiation | Radiation: no internal mammary nodal irradiation<br>* chest wall and supraclavicular+-axillary nodal irradiation (50 Gy in 25 fractions or 43.5Gy in 15 fractions).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease-free survival | failure: relapse of ipsilateral chest wall, axilla, supraclavicular and internal mammary nodal or distant metastasis or contralateral invasive breast cancer or death due to any cause. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | the incidence of death due to any cause. | 5 years | 
| cumulative internal mammary nodal recurrence | ipsilateral internal mammary nodal relapse during follow up. | 5 years | 
| cumulative locoregional recurrence | ipsilateral chest wall, axilla, supraclavicular and internal mammary nodal relapse during follow up. | 5 years | 
| distant metastasis | the incidence of first relapse beyond locoregional region. | 5 years | 
| contralateral non-invasive breast cancer or other malignant tumors | the incidence of contralateral invasive breast cancer or other malignant tumors developed after enrollment. | 5 years | 
| major cardiovascular events | the incidence of death due to coronary heart disease or other heart disease, development of myocardial infarction, coronary recanalization, or hospitalization for a major cardiovascular events (such as heart failure, valvular disease, arrhythmia, unstable angina, or other major cardiovascular event). | 5 years | 
| incidence of adverse events | graded according to radiation therapy oncology group (RTOG) radiation injury criteria and National Cancer Institute CTCAE version 3.0. | 5 years | 
| quality of life | questionaire analysis with European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-BR23 scale | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast neoplasm, mastectomy, radiotherapy, internal mammary node