Partial Breast Re-irradiation for Breast Cancer (BREAST)

Partial Breast Re-irradiation for Breast Cancer Recurrences After Repeat Breast-conserving Surgery With Proton Beam Therapy

Breast cancer is the most common malignancy in women. Breast-conserving surgery (BCS) with adjuvant whole-breast irradiation (WBI) is currently the standard of care in the oncological treatment of primary breast cancer and offers an equivalent alternative to mastectomy. The primary aim of adjuvant radiotherapy (RT) is to improve local control and thus improve overall survival and breast cancer-specific mortality. However, nodal-negative women have a 10-year risk for local recurrences after RT in up to 15.6%. The management of ipsilateral breast cancer recurrence depends on the extent of tumor disease and staging results at the time of recurrence and mastectomy is currently the standard of care for previously irradiated patients. The application of particle therapy using proton beam therapy (PBT) represents an innovative radiotherapeutic technique for breast cancer patients. This trial will be conducted as a prospective single-arm phase II study in 20 patients with histologically proven invasive breast cancer recurrences with negative margins after repeat BCS and with an indication for local re-irradiation. Required time interval will be 1 year after previous RT to the ipsilateral breast. Patients will receive partial breast re-RT with proton beam therapy in 15 once daily fractions up to a total dose of 40.05 GyRBE. The primary endpoint is defined as the cumulative overall occurrence of acute / subacute skin toxicity grade ≥3 within 6 months after the start of re-RT.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancers
• Intervention / Treatment: Radiation: Radiation Therapy

Detailed Description

The therapeutic challenge in re-irradiation involves finding a balance between tumor control and the risk of severe toxicity from cumulative radiation doses in previously irradiated organs. Re-RT options include the use of brachytherapy (BT) ], intraoperative radiotherapy (IORT) or external beam RT with photons or electrons. Depending on the time interval since previous RT and applied technique, high-grade (≥3) toxicity rates for re-RT range from about 9% acute skin to 12 % - 17 % late fibrosis and 1% - 10 % G4 toxicity for BT, late grade 3 fibrosis of 21% for IORT and grade 3 toxicity (skin, esophagitis, wound dehiscence) of 7 - 24% - 35% for EBRT including late breast volume asymmetry in 12%, acute and late grade 4 ulceration (1-2%) and even grade 5 (treatment related deaths) in 1.2%.

The dosimetric profile of PBT with the Bragg Peak offers advantageous physical properties and has proven to be superior to photon-based techniques in respect of dose reduction to adjacent organs-at-risk (OAR) and effective target volume coverage with lower integral doses to the patient's whole body. In addition, this technique could potentially offer higher radiobiological effects and tumor responses [28], which is particularly advantageous in potentially more therapeutically resistant disease biology in breast cancer recurrences. Overall, prospective experience related to re-RT of the ipsilateral breast after recurrences is limited and most commonly involves the technique of invasive multicatheter brachytherapy.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eva Meixner, MD; Phone Number: 0049 6221 56 8201; Email: eva.meixner@med.uni-heidelberg.de

Study Locations

• Germany
  • Heidelberg, Germany, 69120
    • Recruiting
    • University Hospital Heidelberg, Department Radiation Oncology
    • Contact: Adriane Lentz-Hommertgen, PHD; Phone Number: +496221568201; Email: adriane.lentz-hommertgen@med.uni-heidelberg.de
    • Contact: Cornelia Jaekel, PHD; Phone Number: +496221568201; Email: cornelia.jaekel@med.uni-heidelberg.de
    • Principal Investigator: Eva Meixner, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• histologically confirmed recurrent (or new primary) ipsilateral invasive breast cancer or DCIS after prior RT of the ipsilateral breast
• indication for re-irradiation after repeat breast conserving surgery (e.g. lumpectomy, wide excision, …)
• tumor size < 3 cm
• clinically node-negative (cN0)
• negative resection margin (R0)
• time interval: start of re-RT to prior RT ≥ 12 months
• ECOG Performance status ≤ 2
• ability of subject to understand character and individual consequences of the clinical trial
• written informed consent
• ≥18 years of age

Exclusion Criteria:

• distant metastases

  • concomitant chemotherapy (concomitant endocrine hormonal therapy is allowed; sequential chemotherapy is allowed)
  • patients who have not recovered from acute toxicities of prior therapies
  • known carcinoma < 5 years ago (excluding Carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy
  • pregnant or lactating women
  • participation in another competing clinical study or observation period of competing trials
  • history of active connective tissue disorder (i.e. systemic lupus erythematosus, scleroderma, dermatomyositis, xeroderma pigmentosum, …)
  • medical implants, which are at the time of reirradiation not eligible for particle therapy at Heidelberg Ion Beam Therapy Center

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Proton beam therapy	Radiation: Radiation Therapy; proton beam radiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
skin toxicity	Occurrence of overall acute / subacute skin toxicity CTCAE grade 3 or higher (NCI CTCAE version 5.0) assessed.	Within the first 6 months after the start of re-RT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local Tumor control	presence of tumor cells on initial tumor site	At 1, 2 and 5 years after re-RT
Patients Quality of life	quality of life (EORTC QLQ-C30 and the supplementary questionnaire module QLQ-BR42 measuring specific quality of life aspects related to breast cancer treatment)	At 1, 2 and 5 years after re-RT
Regional Tumor control	presence of tumor cells on initial tumor region	At 1, 2 and 5 years after re-RT
Distant Tumor control	presence of tumor cells on distant tumor site	At 1, 2 and 5 years after re-RT
progression-free survival	patients without a tumorprogress	At 1, 2 and 5 years after re-RT
overall survival	alive patients	At 1, 2 and 5 years after re-RT
Quality of life -C30	scores ranging from 0 to 100, with 0 being the lowest score	At 1, 2 and 5 years after re-RT
Quality of life BR-42	Scores ranging from 0 to 100, 0 being the lowest score	At 1, 2 and 5 years after re-RT

Collaborators and Investigators

• Sponsor: University Hospital Heidelberg
• Investigators: Principal Investigator: Juergen Debus, MD, University Hospital Heidelberg

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2025
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: April 16, 2025
• First Submitted That Met QC Criteria: April 24, 2025
• First Posted (Actual): May 1, 2025

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: proton beam; re-irratdiation
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Therapeutics; Radiotherapy
• Other Study ID Numbers: RADONK-2024-BREAST

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No