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

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

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 or breast-conserving surgery.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: internal mammary nodal irradiation; Radiation: no internal mammary nodal irradiation

Detailed Description

Eligible patients are randomized into 2 groups: chest wall/whole breast and supraclavicular nodal +-axillary plus internal mammary nodal irradiation, and chest wall/whole breast 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. Breast cancer patients treated with breast-conserving surgery will receive tumor bed boost.

During and after radiotherapy, the patients are followed and the efficacy and toxicities of radiotherapy are evaluated.

• Study Type: Interventional
• Enrollment (Actual): 2400
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100021
    • Cancer Hospital, Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group Performance Status Scale 0-2
• Histologically confirmed invasive breast cancer
• Underwent total mastectomy/breast-conserving surgery 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

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: internal mammary nodal irradiation; chest wall/whole breast and supraclavicular nodal+-axillary plus internal mammary nodal irradiation	Radiation: internal mammary nodal irradiation; chest wall/whole breast and supraclavicular +-axillary plus internal mammary nodal irradiation (50 Gy in 25 fractions or 43.5Gy in 15 fractions). Patients treated with breast-conserving surgery will receive tumor bed boost. Concurrent boost (60 Gy in 25 fractions over 5 weeks or 49.5 Gy in 15 fractions over 3 weeks) or sequential boost (10 Gy in 5 fractions over 1 week or 8.7 Gy in 3 fractions over 3 days) is optional.
Active Comparator: no-internal mammary nodal irradiation; ipsilateral chest wall/whole breast and supraclavicular +-axillary nodal irradiation	Radiation: no internal mammary nodal irradiation; chest wall/whole breast and supraclavicular+-axillary nodal irradiation (50 Gy in 25 fractions or 43.5Gy in 15 fractions). Concurrent boost (60 Gy in 25 fractions over 5 weeks or 49.5 Gy in 15 fractions over 3 weeks) or sequential boost (10 Gy in 5 fractions over 1 week or 8.7 Gy in 3 fractions over 3 days) is optional.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease-free survival	failure: relapse of ipsilateral chest wall/breast, 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
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
cumulative locoregional recurrence	ipsilateral chest wall/breast, axilla, supraclavicular and internal mammary nodal relapse during follow up.	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Translational Research	Circulating blood markers in relation to efficacy and toxicity	5 year

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Collaborators: Zhejiang Cancer Hospital; Jiangsu Province Hospital of Traditional Chinese Medicine; Fudan University; Peking Union Medical College Hospital; Shanghai Zhongshan Hospital; Henan Cancer Hospital; West China Hospital; Peking University Cancer Hospital & Institute; Jilin Provincial Tumor Hospital; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; Beijing Hospital; Zhongnan Hospital; The First Hospital of Jilin University; Air Force Military Medical University, China; Hebei Medical University Fourth Hospital; Chinese Academy of Medical Sciences, Fuwai Hospital; Tangshan People's Hospital; Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University; Liaoning Cancer Hospital & Institute; Lanzhou University First Hospital; Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center
• Investigators: Study Chair: Ye-xiong Li, M.D, Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Principal Investigator: Shu-lian Wang, M.D, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Publications and helpful links

General Publications

• Zhao XR, Fang H, Tang Y, Hu ZH, Jing H, Liang L, Yan XN, Song YW, Jin J, Liu YP, Chen B, Tang Y, Qi SN, Li N, Lu NN, Men K, Hu C, Zhang YH, Li YX, Wang SL. POstmastectomy radioThErapy in Node-posiTive breast cancer with or without Internal mAmmary nodaL irradiation (POTENTIAL): a study protocol for a multicenter prospective phase III randomized controlled trial. BMC Cancer. 2021 Nov 6;21(1):1185. doi: 10.1186/s12885-021-08852-y.

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2020
• Primary Completion (Actual): November 1, 2025
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: March 19, 2020
• First Submitted That Met QC Criteria: March 23, 2020
• First Posted (Actual): March 25, 2020

Study Record Updates

• Last Update Posted (Estimated): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 10, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: radiotherapy; breast neoplasm; mastectomy; internal mammary node
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: 19/317-2101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Owing to concerns regarding patient privacy.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No