Randomized Study of Elective Regional Lymph Node Irradiation in N1 Breast Cancer

Study Overview
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Brief Summary
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This study evaluates the impact of elective regional lymph node irradiation on N1 breast cancer patients receiving post-lumpectomy radiotherapy and anthracycline plus taxane (AT)-based chemotherapy. We randomly assign patients having one to three metastatic lymph nodes (pN1) after breast-conserving surgery (BCS) and AT-based chemotherapy to undergo either whole-breast and regional nodal irradiation (WB+RNI group) or whole-breast irradiation alone (WBI group).

Detailed Description
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Objective: Compare the effect of post-BCS WBI vs. WB+RNI on disease-free survival in pN1 breast cancer patients who received AT-based chemotherapy. Evaluate the impact of WBI or WB+RNI according to molecular subtype of tumor. Compare the treatment-related toxicities between the WBI and WB+RNI. Compare the patient's quality of life between the WBI and WB+RNI. Outline: This is a a randomized, multi-center, phase III study. Patients are stratified according to molecular subtype of tumor (luminal A vs luminal vs luminal HER2 vs HER2-enriched vs basal-like), axillary lymph node management (sentinel lymph node biopsy [SLN] only vs axillary lymph node dissection+/- SLN) and participating institutions. Patients are randomized to one of two treatment arms. Arm I: Patients receive WB+RNI. Arm II: Patients receive WBI alone. Arm circumference and quality of life (EORTC QLQ-C30 & EORTC QLQ-BR23) are assessed within 2 weeks prior to randomization, during the last week of radiotherapy, at 3 months after completion of radiotherapy, and then annually thereafter for five years. Patients are followed at 3 months after completion of radiotherapy and annually thereafter for seven years.

Official Title
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A Phase III Prospective Randomized Study of Elective Regional Lymph Node Irradiation in Pathologic N1 Breast Cancer Patients Treated With Breast Conserving Surgery

Conditions
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Breast Neoplasm

Intervention / Treatment
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* Radiation: Whole breast irradiation
* Radiation: Whole breast and nodal irradiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven invasive carcinoma of the breast. One to three positive axillary lymph nodes (pN1) proven in pathologic specimen. Prior breast-conserving surgery and post-operative adjuvant chemotherapy including taxane. Administering adjuvant hormonal therapy in cases with hormone receptor-positive tumor. Administering anti-HER2 therapy in cases with HER2-positive tumor. Exclusion Criteria: Metastases in supraclavicular or internal mammary lymph nodes. Metastases in distant organs. Neoadjuvant chemotherapy or hormone therapy before surgery. Not receiving adjuvant anthracycline and taxane. Bilateral breast cancer Previous history of radiotherapy of the ipsilateral breast or supraclavicular lymph nodes. Prior history of other types of cancer, except thyroid cancer, carcinoma in situ of the cervix, or skin cancer.

Ages Eligible for Study
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Minimum Age: 20 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: Whole breast irradiation<br>Post-lumpectomy radiotherapy to the whole breast alone. | Radiation: Whole breast irradiation<br>* Radiotherapy to the whole breast alone.<br>|
| Active Comparator: Whole breast and nodal irradiation<br>Post-lumpectomy radiotherapy to the whole breast and regional lymph node. | Radiation: Whole breast and nodal irradiation<br>* Radiotherapy to the whole breast and regional lymph nodes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival | Disease-free survival | 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival according to molecular subtype | Disease-free survival according to molecular subtype | 5 years | 
| Treatment-related toxicity | acute and chronic toxicities | 5 years | 
| European Organization for Research and Treatment of Cancer (EORTC)-Quality of life. Questionnaire 30 (QLQ-C30) measurement | 1 (Not at all) to 4 (Very much), 1 (Very poor) to 7 (Excellent). For functional and global quality of life scales, higher scores mean a better level of functioning. For symptom-oriented scales, a higher score means more severe symptoms. | 5 years | 
| EORTC Quality of Life Questionnaire - Breast Cancer Module (EORTC QLQ-BR23) measurement | 1 (Not at all) to 4 (Very much). A higher score means more severe symptoms. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adjuvant radiotherapy, Lymphatic irradiation, Taxane, Anthracycline, Prospective study