Breast Re-irradiation After Second Ipsilateral Lumpectomy (BRASIL)

Breast Re-irradiation After Second Ipsilateral Lumpectomy (BRASIL Trial)

The purpose of this research study is to test the safety and possible harms of treating breast cancer with reirradiation, after breast surgery. The researchers want to find out what effects (good and bad) reirradiation has on people who have already received radiation before surgery.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Breast Cancer; HER2-negative Breast Cancer; ER+ Breast Cancer; Cancer of the Breast; Estrogen-receptor-positive Breast Cancer
• Intervention / Treatment: Radiation: Intensity modulated radiation therapy (IMRT)

• Study Type: Interventional
• Enrollment (Estimated): 114
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Youssef Zeidan, M.D., Ph.D.; Phone Number: (561) 955-5966; Email: youssef.zeidan@baptisthealth.net
• Study Contact Backup: Name: MCI Multisite Research Program; Email: MCIMultiSiteResearch@baptishealth.net

Study Locations

• United States
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Recruiting
      • Lynn Cancer Institute at Baptist Health, Inc.
      • Contact: Youssef Zeidan, M.D., Ph.D.; Phone Number: (561) 955-5966; Email: youssef.zeidan@baptisthealth.net
      • Contact: MCI Multisite Research Program; Email: MCIMultiSiteResearch@baptishealth.net
    • Miami, Florida, United States, 33176
      • Recruiting
      • Miami Cancer Institute at Baptist Health, Inc.
      • Contact: MCI Multisite Research Program; Email: MCIMultiSiteResearch@baptishealth.net
      • Contact: Joseph Panoff, M.D.; Phone Number: (786) 596-2000; Email: josephpa@baptisthealth.net

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosed with ER+HER2- breast cancer
• Provision of signed and dated ICF
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Age ≥ 40 years
• Oncotype < 26 (postmenopausal) <16 (premenopausal), Low, or Ultra-Low index.
• Minimum interval of 18 months from last breast radiotherapy session.
• Prior radiation therapy in the form of brachytherapy, external beam MV photons, protons or intraoperative radiation are allowed with an upper total dose limit of 68 Gy (EQD2) for those patients with prior records available.
• Ipsilateral recurrence, unifocal < 3 cm with negative margins, N0, Tis and invasive (pathological staging)
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Planning target volume: whole breast (PTV: WB) ratio < 1/2
• Life expectancy > 12 months
• Individuals able to become pregnant: agreement to use highly effective contraception starting at screening through treatment, and for 1 year after the end of PBI. Should a participant become pregnant or suspect that they are pregnant while participating in this study, they should notify the treating physician immediately.

A person able to become pregnant is any person assigned female at birth (regardless of gender identity, sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

1. Has not undergone a hysterectomy or bilateral oophorectomy; or
2. Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has not had menses at any time during the preceding 12 consecutive months)

Exclusion Criteria:

• BRCA1/2 mutation or any other receptor subtypes
• Individuals assigned male at birth with breast cancer
• Pregnancy or breastfeeding
• Skin involvement
• Distant metastasis
• Patients with initial high-risk triple negative or HER-2 enriched breast cancer will be excluded from the trial. However, if the initial subtype is not known, patients will still be allowed to enroll, and the initial primary tumor information will be recorded as missing on the clinical forms.
• Other malignancies (except skin)
• Connective tissue disorder (e.g., scleroderma, lupus)
• Any other condition that may put a participant at higher risk, at the discretion of the investigator.

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: Partial Breast Irradiation (PBI)	Radiation: Intensity modulated radiation therapy (IMRT); 40 Gy total in 15 consecutive weekday sessions to the partial breast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of grade 3 or higher treatment-related adverse events (AEs)	Adverse events will be collected using Common Terminology Criteria for Adverse Events version 5 (CTCAE v5) starting from the first radiation treatment. Grade 1 AEs are considered mild, grade 2 AEs are considered moderate, grade 3 AEs are considered severe, grade 4 AEs are considered life-threatening, and grade 5 AEs are considered fatal. The percentage of participants experiencing grade 3 or higher treatment-related AEs will be calculated.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local recurrence-free survival (LRFS)	Local recurrence is defined as tumor recurrence in the reirradiated region. LRFS is defined as time from the start of radiation treatment to local recurrence or death, whichever occurs first, and will be estimated by Kaplan-Meier method. Participants who do not have local recurrence and are still alive will be censored to their final follow-up date.	5 years
Overall survival (OS)	OS is defined as the time from the start of radiation treatment to death and will be estimated by Kaplan-Meier method. Participants who are still alive will be censored to their final follow-up date.	5 years
Distant metastasis-free survival (DMFS)	Distant metastasis is defined as cancer spreading to other areas of the body. DMFS is defined as the time from the start of radiation treatment to time of distant metastasis or death and will be estimated by Kaplan-Meier method. Participants who do not have distant metastasis and are still alive will be censored to their final follow-up date.	5 years
Mastectomy-free survival (MFS)	MFS is defined as the time from the start of radiation treatment to mastectomy or death, whichever occurs first, and will be estimated by Kaplan-Meier method. Participants who have not had a mastectomy and are still alive will be censored to their final follow-up date.	5 years
Change in patient-rated cosmesis	Assessed using the National Surgical Adjuvant Breast and Bowel Project (NSABP) B39.0 questionnaire. Physical appearance. 22 questions, rated 1 (no difference between breasts) to 4 (large difference). Range 22-88 (worse). Recovery. 8 questions, rated 0 (not at all) to 10 (a lot). In 7 questions, higher is worse; scoring will be reversed for 1 item. Range 0-80 (worse). Feelings. 4 questions, rated 1 (all the time) to 5 (none of the time). Lower is better for 2 but worse for 2. Scoring for 2 items will be reversed. 4 questions related to pain rated from 0 (no pain) to 10 (worst pain). Range 0-40 (worse). One question is about pain treatment. Bothered. 27 questions, rated 0 (not at all) to 4 (very much). Range 0 -108 (worse). Satisfaction. Appearance of the treated breast rated from 1 (excellent) to 4 (poor). Satisfaction rated on a 5-item scale from totally satisfied to totally dissatisfied. Breast size before and after treatment: left larger, same, right larger.	Over 5 years

Collaborators and Investigators

• Sponsor: Youssef Zeidan
• Collaborators: Boca Raton Regional Hospital Foundation
• Investigators: Principal Investigator: Youssef Zeidan, M.D., Ph.D., Lynn Cancer Institute at Baptist Health, Inc.

Publications and helpful links

General Publications

• Olivotto IA, Whelan TJ, Parpia S, Kim DH, Berrang T, Truong PT, Kong I, Cochrane B, Nichol A, Roy I, Germain I, Akra M, Reed M, Fyles A, Trotter T, Perera F, Beckham W, Levine MN, Julian JA. Interim cosmetic and toxicity results from RAPID: a randomized trial of accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy. J Clin Oncol. 2013 Nov 10;31(32):4038-45. doi: 10.1200/JCO.2013.50.5511. Epub 2013 Jul 8.
• Arthur DW, Winter KA, Kuerer HM, Haffty B, Cuttino L, Todor DA, Anne PR, Anderson P, Woodward WA, McCormick B, Cheston S, Sahijdak WM, Canaday D, Brown DR, Currey A, Fisher CM, Jagsi R, Moughan J, White JR. Effectiveness of Breast-Conserving Surgery and 3-Dimensional Conformal Partial Breast Reirradiation for Recurrence of Breast Cancer in the Ipsilateral Breast: The NRG Oncology/RTOG 1014 Phase 2 Clinical Trial. JAMA Oncol. 2020 Jan 1;6(1):75-82. doi: 10.1001/jamaoncol.2019.4320.
• Arthur DW, Winter KA, Kuerer HM, Haffty BG, Cuttino LW, Todor DA, Simone NL, Hayes SB, Woodward WA, McCormick B, Cohen RJ, Sahijdak WM, Canaday DJ, Brown DR, Currey AD, Fisher CM, Jagsi R, White J. NRG Oncology-Radiation Therapy Oncology Group Study 1014: 1-Year Toxicity Report From a Phase 2 Study of Repeat Breast-Preserving Surgery and 3-Dimensional Conformal Partial-Breast Reirradiation for In-Breast Recurrence. Int J Radiat Oncol Biol Phys. 2017 Aug 1;98(5):1028-1035. doi: 10.1016/j.ijrobp.2017.03.016. Epub 2017 Mar 18.

Helpful Links

• Lynn Cancer Institute at Baptist Health, Inc.
• Miami Cancer Institute at Baptist Health, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2033

Study Registration Dates

• First Submitted: March 5, 2025
• First Submitted That Met QC Criteria: March 5, 2025
• First Posted (Actual): March 10, 2025

Study Record Updates

• Last Update Posted (Estimated): November 13, 2025
• Last Update Submitted That Met QC Criteria: November 12, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Neoplasms; Breast Neoplasms; Therapeutics; Radiotherapy; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy, Intensity-Modulated
• Other Study ID Numbers: LCI-2023-ZEI-001

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
• product manufactured in and exported from the U.S.: No