The T-REX Trial: Tailored Regional External Beam Radiotherapy in Clinically Node-negative Breast Cancer Patients With 1-2 Sentinel Node Macrometastases. (T-REX)

May 8, 2026 updated by: Region Skane

The T-REX-Trial: Tailored Regional External Beam Radiotherapy in Clinically Node-negative Breast Cancer Patients With 1-2 Sentinel Node Macrometastases; an Open, Multicenter, Randomized Non-inferiority Phase 3-trial.

T-REX is a randomized multicenter, non-inferiority trial.

Aim: To evaluate whether regional radiotherapy may safely be omitted in clinically node negative breast cancer patients with one or two sentinel node macrometastases and an estrogen receptor positive, HER2-negative tumor. Leading to an improved quality of life and reduced side effects, without worsening recurrence free survival at five years.

Intervention: Patients will be randomized to locoregional radiotherapy towards the breast/chestwall and regional lymph nodes vs. to a de-escalated radiotherapy.

In the intervention arm no lymph node irradiation will be given. Radiotherapy is still given to the remaining breast after breast conserving surgery, but no radiotherapy is given after mastectomy.

Sample size: 1350 patients

Primary end-point: Recurrence free survival at five years.

Gene expression analysis: For all patients gene expression analysis for the gene signatures ARTIC, POLAR and OncotypeDX will be performed and related to risk of recurrence and benefit of adjuvant radiotherapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

In this multicenter, prospective randomized trial clinically node-negative breast cancer patients with 1-2 macrometastases in their sentinel lymph node biopsy, and an estrogen receptor positive, HER2-negative tumor, will be randomly assigned to either receive adjuvant locoregional radiotherapy, or no regional radiotherapy.

The main aim is to evaluate whether regional radiotherapy may safely be omitted in patients with limited lymph node metastasis and an estimated low risk of locoregional recurrence. Recurrence free survival after five years is the primary outcome, which for non-inferiority should not worsen more than 4.5 percentage units. Secondary outcomes are locoregional recurrence, regional nodal recurrence, new contralateral BC, distant recurrence free survival, overall survival, non-breast malignancies, cardiac disease, arm morbidity, and health-related quality of life.

Target volumes include:

Standard arm - The remaining breast/chest wall, axillary lymph node levels I-III, the supraclavicular lymph nodes (level IV), the interpectoral lymph nodes and in patients with a medial/central tumor also the internal mammary lymph nodes.

Intervention arm - The remaining breast after breast conserving surgery. No radiotherapy after mastectomy

Study Type

Interventional

Enrollment (Estimated)

1350

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Finland
      • Helsinki, Finland
        • Recruiting
        • Helsinki University Hospital
        • Contact:
      • Lahti, Finland
        • Not yet recruiting
        • Lahti Hospital
        • Contact:
      • Turku, Finland
        • Not yet recruiting
        • Turku University Hospital
        • Contact:
  • Norway
      • Bergen, Norway
        • Recruiting
        • Bergen
        • Contact:
          • Ingvil Mjaaland
      • Bodø, Norway
        • Not yet recruiting
        • Bodø
        • Contact:
          • Sara Alkner
      • Gjøvik, Norway
        • Recruiting
        • Gjövik
        • Contact:
          • Ingvil Mjaaland
      • Kristiansand, Norway
        • Recruiting
        • Kristiansand
        • Contact:
          • Ingvil Mjaaland
      • Oslo, Norway
        • Recruiting
        • Oslo
        • Contact:
          • Ingvil Mjaaland
      • Stavanger, Norway
        • Recruiting
        • Stavanger
        • Contact:
          • Ingvil Mjaaland
      • Tromsø, Norway
        • Recruiting
        • Tromsø
        • Contact:
          • Ingvil Mjaaland
      • Trondheim, Norway
        • Recruiting
        • Trondheim
        • Contact:
          • Ingvil Mjaaland
      • Ålesund, Norway
        • Recruiting
        • Ålesund
        • Contact:
          • Ingvil Mjaaland
  • Sweden
      • Borås, Sweden
        • Recruiting
        • Region Västragötaland
        • Contact:
          • Sara Alkner
      • Eskilstuna, Sweden, 24751
      • Gothenburg, Sweden
        • Recruiting
        • Region Västra Götaland
        • Contact:
          • Per Karlsson
      • Gävle, Sweden
        • Recruiting
        • Region Gävleborg
        • Contact:
          • Sara Alkner
      • Halmstad, Sweden
        • Recruiting
        • Region Halland
        • Contact:
          • Sara Alkner
      • Jönköping, Sweden
        • Recruiting
        • Region Jönköping
        • Contact:
          • Sara Alkner
      • Kalmar, Sweden
        • Recruiting
        • Region Kalmar län
        • Contact:
          • Sara Alkner
      • Karlstad, Sweden
        • Recruiting
        • Region Värmland
        • Contact:
          • Sara Alkner
      • Linköping, Sweden
        • Recruiting
        • Region Östergötland
        • Contact:
          • Sara Alkner
      • Lund, Sweden
      • Skövde, Sweden
        • Recruiting
        • Region Västragötaland
        • Contact:
          • Sara Alkner
      • Stockholm, Sweden
        • Recruiting
        • Region Stockholm
        • Contact:
          • Sara Alkner
      • Sundsvall, Sweden
        • Recruiting
        • Region Västernorrland
        • Contact:
          • Sara Alkner
      • Umeå, Sweden
        • Recruiting
        • Region Västerbotten
        • Contact:
          • Sara Alkner
      • Uppsala, Sweden
        • Not yet recruiting
        • Region Uppsala
        • Contact:
          • Sara Alkner
      • Vaxjo, Sweden
        • Recruiting
        • Region Kronoberg
        • Contact:
          • Sara Alkner
      • Västerås, Sweden
        • Recruiting
        • Region Västmanland
        • Contact:
          • Sara Alkner
      • Örebro, Sweden
        • Recruiting
        • Region Örebro
        • Contact:
          • Sara Alkner

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Primary unifocal or multifocal invasive breast cancer T1-T2.
  2. Clinically N0.
  3. Macrometastasis (>2mm) in 1-2 lymph nodes at sentinel node biopsy.
  4. Oral and written consent.
  5. Age ≥ 18 years.
  6. All resection margins are tumor free (no tumor on ink).
  7. Primary tumor ER-positive, HER2-negative.

Exclusion Criteria:

  1. Regional or distant metastases outside the ipsilateral axilla.
  2. Previous RT towards the planned target area, i.e. the ipsilateral chest/lymph nodes.
  3. Neoadjuvant systemic therapy.
  4. Axillary lymph node dissection or other previous axillary surgery on the affected side.
  5. Prior history of invasive breast cancer.
  6. Pregnancy.
  7. Bilateral invasive breast cancer.
  8. Contraindication for radiotherapy or systemic treatment.
  9. Inability to absorb or understand the contents of the informed consent form; for example, through disability, inadequate language skills or dementia.
  10. Other invasive cancer within 5 years prior to breast cancer diagnosis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Standard
Radiotherapy to the remaining breast after breast conserving surgery or chest wall after mastectomy, and regional axillary lymph node levels I-IV. Internal mammary nodes are included in the target volume if the tumor has a central/medial localization in the breast.
Experimental: Intervention
No regional radiotherapy. Radiotherapy is given to the remaining breast after breast conserving surgery. Chest wall radiotherapy after mastectomy only in case of wide spread multifocality.
Radiation: De-escalation
No regional radiotherapy. Radiotherapy is given to the remaining breast after breast conserving surgery. Chest wall radiotherapy after mastectomy only in case of wide spread multifocality.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Recurrence Free Survival
Time Frame: Five years
Five years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Five years
Five years
Locoregional recurrence
Time Frame: Five years
Five years
Regional nodal recurrence
Time Frame: Five years
Five years
New contralateral breast cancer
Time Frame: Five years
Five years
Distant recurrence free survival
Time Frame: Five years
Five years
Arm morbidity
Time Frame: Five years
Assessed by questionnaires completed by study participants digitally or on paper between randomization and start of RT, and after 1, 3, and 5 years. The questionnaire used is the Lymphedema Functioning, Disability and Health Questionnaire (Lymph-ICF) developed by Devoogdt in 2011.
Five years
Health-related quality of life
Time Frame: Five years
Assessed by the questionnaire EORTC QLQ-C-30 completed by study participants between randomization and RT, and after 1, 3, and 5 years.
Five years
Health-related quality of life
Time Frame: Five years
Assessed by the questionnaire BR-23 completed by study participants between randomization and RT, and after 1, 3, and 5 years.
Five years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Region Skane

Collaborators

Exact Sciences Corporation

Investigators

  • Principal Investigator: Sara Alkner, Associate professor, Lunds Universitet

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 17, 2023

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

December 31, 2033

Study Registration Dates

First Submitted

November 18, 2022

First Submitted That Met QC Criteria

November 29, 2022

First Posted (Actual)

December 2, 2022

Study Record Updates

Last Update Posted (Actual)

May 11, 2026

Last Update Submitted That Met QC Criteria

May 8, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-05093-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be made available upon request by the T-REX study group through primary investigator Sara Alkner (sara.alkner@med.lu.se) as specified below.

IPD Sharing Time Frame

The above information is available. IPD will be shared upon reasonable request after publication of the main endpoint. No end date.

IPD Sharing Access Criteria

Study protocol, Statistical Analysis Plan, Informed Consent Form and Clinical Study Report will be available to all interested.

Deidentified participant data, and access to biological material, could be made available to researchers who provide a methodologically sound proposal with all prepared documents for ethical approval to the T-REX study group / the T-REX biobank group through primary investigator Sara Alkner (sara.alkner@med.lu.se).

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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