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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Neoplasm
• Intervention / Treatment: Radiation: Whole breast irradiation; Radiation: Whole breast and nodal irradiation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 827
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

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
Experimental: Whole breast irradiation; Post-lumpectomy radiotherapy to the whole breast alone.	Radiation: Whole breast irradiation; Radiotherapy to the whole breast alone.
Active Comparator: Whole breast and nodal irradiation; Post-lumpectomy radiotherapy to the whole breast and regional lymph node.	Radiation: Whole breast and nodal irradiation; Radiotherapy to the whole breast and regional lymph nodes.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Collaborators: Ministry of Health, Republic of Korea; Korean Radiation Oncology Group
• Investigators: Study Chair: Won Park, MD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2017
• Primary Completion (Estimated): December 30, 2029
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: August 30, 2017
• First Submitted That Met QC Criteria: August 30, 2017
• First Posted (Actual): September 1, 2017

Study Record Updates

• Last Update Posted (Actual): November 27, 2023
• Last Update Submitted That Met QC Criteria: November 22, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Anthracycline; Prospective study; Taxane; Adjuvant radiotherapy; Lymphatic irradiation
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: SMC 2017-01-085-001

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