Single-fraction APBI for Early-stage Breast Cancer With Favorable Histological Subtypes (Breast-1F) (Breast-1F)

November 26, 2025 updated by: Andrei Fodor, MD, IRCCS San Raffaele

Accelerated Partial Breast Irradiation in One Fraction for Patients With Early-stage Disease and Favorable Histological Subtypes (Breast-1F).

This is a prospective, randomized, monocentric, non-inferiority interventional clinical study comparing an Accelerated Partial Breast Irradiation (APBI) for the surgical bed of early-stage breast cancer patients with favorable histological subtypes, using stereotactic radiotherapy in a single dose of 15.5 Gy with Simultaneous Integrated Boost (SIB) to 21 Gy (study treatment, delivered in a single fraction) versus multifractionated radiotherapy of 30 Gy in 5 fractions (standard treatment, delivered in 5 fractions).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The project refers to a study on patients with early-stage breast cancer with pathological Tumor stage (pT) from in situ (pTis) to pT2 up to 3 cm in diameter, and pathological/clinical nodal stage p/cN0, and favorable histology (Luminal A and Luminal B human epidermal growth factor receptor 2 (HER2)-negative subtypes), comparing an APBI treatment delivered with stereotactic radiotherapy to the Planning Target Volume (PTV) of the tumor bed of the breast with a total dose (TD) of 15.5 Gy in one fraction, with simultaneous integrated boost (SIB) to a TD of 21 Gy to the Gross Tumor Volume (GTV) represented by tumor bed, versus 30 Gy in 5 consecutive fractions to the PTV of the tumor bed, according to the standard APBI protocol of the department (Florence protocol).

Study Type

Interventional

Enrollment (Estimated)

311

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

  • Italy
      • Milan, Italy, 20132
        • Recruiting
        • IRCCS San Raffaele Scientific Institute
        • Contact:
        • Contact:

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Histological diagnosis of breast cancer
  2. Patients aged ≥40 years
  3. Signed informed consent
  4. Stage pTis-T2, up to 3 cm in the greatest diameter
  5. Luminal A and Luminal B HER2-negative histological subtypes
  6. Negative surgical margins (≥ 0.2 cm)
  7. Negative lymph nodes at sentinel lymph node biopsy, or alternatively with imaging tests (Positron Emission Tomography (PET)/Computed Tomography (CT) and/or axillary ultrasound, and/or breast Magnetic Resonance Imaging (MRI) with and without contrast), or, in rare cases, where still performed, with axillary dissection
  8. Clinical M0 (PET/CT and/or bone scintigraphy and/or abdomen-pelvis CT with and without contrast in suspected patients), within the previous 3 months.
  9. Performance Status (PS) Eastern Cooperative Oncology Group (ECOG) ≤2
  10. No prior thoracic radiotherapy
  11. Fertile women using contraception methods initiated during oncological treatment.

Exclusion Criteria:

  1. Patients aged < 40 years
  2. Tumors > 3 cm
  3. Multicentric tumors
  4. Positive or close surgical margins (<0.2 cm)
  5. Lobular carcinoma
  6. Negative hormone receptors
  7. HER2-positive
  8. BReast CAncer (BRCA) genes BRCA1 and/or BRCA2 positive (only if known)
  9. Severe systemic diseases
  10. Psychiatric or other disorders that may prevent the patient from signing informed consent
  11. Previous invasive cancer, except for skin cancer (excluding melanoma) unless the patient has been disease-free for at least 3 years (e.g., carcinoma in situ of the oral cavity or bladder)
  12. Collagen or autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, scleroderma, Sjogren's syndrome)
  13. Lymph node disease (N1)
  14. Evidence of distant metastasis (M1)
  15. Contraindication to systemic treatment
  16. Pregnant women
  17. Non-compliance with the dose limits established in the treatment plan

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
Experimental: Arm 1- Single-fraction APBI
Patients in the study (randomized to arm 1) will be treated with a total dose (TD) of 15.5 Gy to the Planning Tumor Volume (PTV) with simultaneous integrated boost (SIB) to a TD of 21 Gy to the tumor bed. For each patient, a stereotactic radiotherapy treatment plan will be created to ensure adequate coverage of the treatment volumes and the tolerability of the Organs At Risk (OAR). Specific, already validated dose-volume constraints will be applied for the evaluation of OARs. The dose-volume histogram (DVH) for the Gross Tumor Volume (GTV), Clinical Target Volume (CTV), PTV, and OAR will be calculated in order to achieve the best optimization in terms of tolerability and efficacy.
Radiation: Adjuvant single-fraction accelerated partial breast irradiation
Experimental arm (arm 1-single-fraction APBI) patients will be treated to a total dose (TD) of 15.5 Gy to the PTV with a simultaneous integrated boost (SIB) to a TD of 21 Gy to the tumor bed, while arm 2-five-fractions APBI patients with 30 Gy/ 5 fractions to PTV.
Other Names:
  • Ultrahypofractionated Radiotherapy
Active Comparator: Arm 2- Five-fractions APBI
Patients randomized to arm 2 will be treated according to the standard APBI protocol of our department (Florence protocol), delivering a TD of 30 Gy in 5 fractions to the tumor bed.
Radiation: Adjuvant single-fraction accelerated partial breast irradiation
Experimental arm (arm 1-single-fraction APBI) patients will be treated to a total dose (TD) of 15.5 Gy to the PTV with a simultaneous integrated boost (SIB) to a TD of 21 Gy to the tumor bed, while arm 2-five-fractions APBI patients with 30 Gy/ 5 fractions to PTV.
Other Names:
  • Ultrahypofractionated Radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ipsilateral Breast Tumor Recurrence (IBTR)
Time Frame: 5 years
To demonstrate the non-inferiority of local control (ipsilateral breast tumor recurrence - IBTR) of the study treatment (delivered in a single-fraction APBI) compared to the department's standard APBI treatment (delivered in 5 fractions).
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute toxicity
Time Frame: 3 months
Acute toxicity grade ≥3 as the maximum toxicity value within 1 month and 3 months after the completion of radiotherapy treatment evaluated with RTOG/EORTC scale with 4 grades, from 0 no change to 4, worst toxicity
3 months
Cosmesis
Time Frame: 5 years
Cosmetic results evaluated with Harvard scale. It assesses the global esthetic appearance of the breast, categorized as Excellent, Good, Fair, or Poor
5 years
Acute toxicity interim analysis
Time Frame: 3 months
An interim analysis of acute toxicity (with RTOG/EORTC andf CTCAE v5.0 scales) will be performed for the first 120 patients
3 months
Late toxicity interim analysis
Time Frame: 42 months
An interim analysis of late toxicity (with RTOG/EORTC andf CTCAE v5.0 scales) will be performed for the first 120 patients
42 months
Local relapse interim analysis
Time Frame: 42 months
An interim analysis of local relapse rate will be performed for the first 120 patients
42 months
Acute toxicity
Time Frame: 1 month
Acute toxicity grade ≥3 as the maximum toxicity value within 1 month and 3 months after the completion of radiotherapy treatment evaluated with Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) scale with 4 grades, from 0 no change to 4, worst toxicity
1 month
Late toxicity
Time Frame: 5 years
Late toxicity evaluated with RTOG/EORTC and Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale, with 5 grades, from 0 = no change, to 5 = death for toxicity
5 years
Local Control
Time Frame: 5 years
Local control of the treated site expressed in terms of local recurrence rate
5 years
Local Relapse-Free Survival (LRFS)
Time Frame: From the date of radiotherapy end until the date of local relapse, assessed up to 5 years
Time to local recurrence
From the date of radiotherapy end until the date of local relapse, assessed up to 5 years
Regional Relapse-Free Survival (RRFS)
Time Frame: From the date of radiotherapy end until the date of regional relapse, assessed up to 5 years
Time to regional (nodal) recurrence
From the date of radiotherapy end until the date of regional relapse, assessed up to 5 years
Distant Metastasis-Free Survival (DMFS)
Time Frame: From the date of radiotherapy end until the date of distant metasis diagnosis, assessed up to 5 years
Time to distant (metastatic) relapse
From the date of radiotherapy end until the date of distant metasis diagnosis, assessed up to 5 years
Disease-Free Survival (DFS)
Time Frame: From the date of radiotherapy end until the date of first, any ( local, regional, distant) relapse, assessed up to 5 years
Time to first any relapse: local, regional or distant
From the date of radiotherapy end until the date of first, any ( local, regional, distant) relapse, assessed up to 5 years
Breast Cancer Specific Survival (BCSS)
Time Frame: From the date of radiotherapy end until the date of death from breast cancer, assessed up to 5 years
Time until death from breast cancer
From the date of radiotherapy end until the date of death from breast cancer, assessed up to 5 years
Overall Survival (OS)
Time Frame: From the date of radiotherapy end until the date of death from any cause, assessed up to 5 years
Time until death from any cause
From the date of radiotherapy end until the date of death from any cause, assessed up to 5 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Radiomics
Time Frame: 5 years
Evaluation of radiomic characteristics: Mathematical extraction of the spatial distribution of signal intensities and pixel interrelationships of medical images of the patients, to quantify textural information resampled according to International Biomarker Standardization Initiative (IBSI).
5 years
Modeling of organ movement
Time Frame: 5 days
Modeling of organ movement during treatment
5 days
Incidence of Treatment-Emergent Adverse Events as assessed with breast tumor specific quality of life questionnaires
Time Frame: 5 years
Survey with the questionnaire of European Organisation for Research and Treatment of Cancer (EORTC) Quality of life of brain tumor patients (EORTC QLQ BR42) which contains 42 questions on patients' quality of life with answers from 1, lowest grade, to 4, highest grade
5 years
Predictive factors for toxicity, disease progression and death
Time Frame: 5 years
Identification of clinical, imaging, and laboratory prognostic factors for an aggressive phenotype of Luminal A and Luminal B HER2-negative breast cancer and for toxicity
5 years

Collaborators and Investigators

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

Sponsor

IRCCS San Raffaele

Investigators

  • Principal Investigator: Andrei Fodor, MD, IRCCS San Raffaele Scientific Institute

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)

July 25, 2025

Primary Completion (Estimated)

June 30, 2029

Study Completion (Estimated)

June 30, 2035

Study Registration Dates

First Submitted

April 19, 2025

First Submitted That Met QC Criteria

April 19, 2025

First Posted (Actual)

April 27, 2025

Study Record Updates

Last Update Posted (Estimated)

December 4, 2025

Last Update Submitted That Met QC Criteria

November 26, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Breast-1F

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The data that support the findings of this study (anonymized individual participant data) are available on request from the corresponding author to researchers who provide a methodologically sound proposal. Requests made to the corresponding author will be evaluated by the Lombardy Territorial Ethics Committee 1

IPD Sharing Time Frame

for 5 years after the end of the study

IPD Sharing Access Criteria

request from the corresponding author approved by the Lombardy Territorial Ethics Committee

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ANALYTIC_CODE
  • 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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