EXamining PErsonalised Radiation Therapy for Low-risk Early Breast Cancer

NCT ID: NCT02889874

Last Updated: 2025-09-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 1167 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-21
• Study Completion Date: 2028-04-30

Brief Summary

This is a randomised, phase III, non-inferiority trial evaluating radiation therapy versus observation following breast conserving surgery and planned endocrine therapy in patients with stage I breast cancer of luminal A subtype defined using the Prosigna (PAM50) Assay.

Detailed Description

Radiation therapy (RT) after breast conserving surgery to improve local control and survival is the current standard of care for patients with early breast cancer. However, breast cancer is a heterogeneous disease, and the absolute benefit of RT in individual patients varies substantially. Thus, a pressing priority in contemporary breast cancer management is to tailor RT utilisation to the individual recurrence risks by identifying patients who are unlikely to benefit from RT, thereby avoiding the morbidity and costs of over-treatment.

It is recognised that selected patients with early breast cancer are unlikely to derive benefits from RT after breast conserving surgery. However, randomised trials have not consistently identified patients who may safely omit RT using conventional clinical-pathologic characteristics.

Breast cancer intrinsic subtypes distinguished by gene expression profiling are shown to be associated with distinct clinical outcomes. There is substantial evidence supporting the clinical validity of multigene assays including the PAM50-based Prosigna Assay that identifies intrinsic subtypes and generates a Risk of Recurrence score (ROR) to quantify individual risks of distant relapse. Multigene assays are increasingly integrated into clinical practice to inform chemotherapy decision, highlighting their substantial practice changing potential in personalising the use of RT for early breast cancer.

A recent analysis of archived tumour specimens of 1,308 patients with early breast cancer has shown significant associations between local recurrence risk and the PAM50-defined intrinsic subtypes and ROR score. EXPERT presents a unique opportunity of clinical and public health importance to optimise personalised local therapy for early breast cancer through precise, individualised quantification of local recurrence risk to identify low-risk patients for whom RT after breast conserving surgery may be safely omitted.

Conditions

Early Stage Breast Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A: Radiation Therapy & endocrine therapy

Patients randomized to Arm A will receive standard radiation therapy and adjuvant endocrine therapy (standard of care).

Group Type: NO_INTERVENTION

No interventions assigned to this group

B: No Radiation Therapy (ET only)

Patients randomized to Arm B will not receive radiation therapy (omission of radiation therapy) and receive adjuvant endocrine therapy only.

Group Type: EXPERIMENTAL

Omission of radiation therapy

Intervention Type: RADIATION

Omission of radiation therapy (adjuvant endocrine therapy only).

Interventions

Omission of radiation therapy

Omission of radiation therapy (adjuvant endocrine therapy only).

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

1. Female patients aged ≥ 50 years of any menopausal status.

2. Primary tumour characteristics as assessed by conventional histopathology:

• Unifocal histologically confirmed invasive breast carcinoma
• Maximum microscopic size ≤2 cm
• Grade 1 or 2 histology
• ER and PR positive in ≥10% of tumour cells in either the biopsy or breast conserving surgical specimen
• HER2 negative on IHC (score 0 or 1+) or in situ hybridisation (ERBB2-amplification Ratio ERBB2/centromeres <2.0 or mean gene copy number <6). Equivocal IHC score (2+) must be assessed by ISH.

3. Primary tumour must be resected by breast conserving surgery with microscopically negative margins for invasive carcinoma and any associated ductal carcinoma in situ (no cancer cells adjacent to any inked edge/surface of specimen) or re-excision showing no residual disease.

4. Histologically confirmed negative nodal status determined by sentinel node biopsy or axillary dissection. Patients with pN0 (i+) disease are eligible for study participation (malignant cells ≤0.2 mm in regional lymph node(s) detected by hematoxylin-eosin (H&E) stain or IHC, including isolated tumour cells).

5. No evidence of distant metastasis.

6. Eligible for and willing to have adjuvant endocrine therapy.

7. ECOG performance status 0-2.

8. Availability of FFPE tumour block for Prosigna (PAM50) Assay.

For randomization to the study, patients must fulfill all of the following criteria:

1. Primary tumour characteristics as assessed by Prosigna (PAM50) Assay:

• Luminal A intrinsic subtype
• ROR score ≤60

Exclusion Criteria

Any one of the following is regarded as a criterion for exclusion from the study:

1. Primary tumour characteristics:

• Presence of multifocal or multicentric invasive carcinoma or ductal carcinoma in situ;
• Evidence of clinical or pathologic T4 disease (extension to the chest wall, oedema or ulceration of skin, satellite skin nodules, inflammatory carcinoma);
• The invasive component of the primary tumour is present as micro-invasion only;
• Grade 3 histology;
• Presence of lymphovascular invasion

2. Contra-indication or unwillingness to have adjuvant endocrine therapy.

3. Planned to receive adjuvant chemotherapy or biologic therapy after breast cancer surgery, i.e. any systemic therapy other than endocrine therapy is not permitted. Any therapy unrelated to cancer is permitted at the discretion of investigators.

4. Treated with neoadjuvant endocrine therapy, chemotherapy or biologic therapy prior to breast cancer surgery.

5. Prior breast or thoracic RT for any condition.

6. Pre-operative breast imaging evidence of disease aside from the primary carcinoma resected by breast conserving surgery.

7. Concurrent invasive breast carcinoma or ductal carcinoma in situ (synchronous or metachronous).

8. Prior diagnosis of invasive breast carcinoma or ductal carcinoma in situ in either breast irrespective of disease free interval.

9. A diagnosis of non-breast malignancy <5 years prior to randomisation with the following exceptions:

• Patients who are diagnosed with carcinoma in situ of cervix, endometrium or colon; melanoma in situ; and basal or squamous cell carcinoma of the skin at any time prior to randomisation are not excluded from study participation.
• Patients who are diagnosed with other non-breast malignancy ≥5 years prior to randomisation and without evidence of disease recurrence are not excluded from study participation.

10. Significant comorbidity precluding definitive RT for breast cancer (e.g. cardiovascular or pulmonary disease, scleroderma, systemic lupus erythematosus).

11. Life expectancy <10 years.

12. Documented mutation of BRCA1, BRCA2 or TP53, or at high genetic risk of breast cancer.

13. Pregnant or lactating patients.

14. Inability to be registered to the study ≤8 weeks after the last surgical procedure for breast cancer.

15. Inability to commence RT (if randomised to receive RT) no later than 12 weeks from the last surgical procedure for breast cancer.

16. Inability to provide written informed consent.

17. Psychiatric, addictive, or any disorder that precludes compliance with protocol requirements.

• Minimum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Breast International Group

OTHER

Sponsor Role: collaborator

ETOP IBCSG Partners Foundation

NETWORK

Sponsor Role: collaborator

Breast Cancer Trials, Australia and New Zealand

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Heath Badger

Role: STUDY_DIRECTOR

Breast Cancer Trials, Australia and New Zealand

Boon H Chua, Prof

Role: STUDY_CHAIR

Prince of Wales Hospital

Locations

Sanatorio Britanico Rosariio

Rosario, Santa Fe Province, Argentina

Instituto de Oncologia de Rosario

Santa Fe, , Argentina

Clinica Viedma

Sarmiento, , Argentina

The Canberra Hospital

Canberra, Australian Capital Territory, Australia

Macarthur Cancer Therapy Centre

Campbelltown, New South Wales, Australia

The Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

St Vincent's Hospital, Sydney

Darlinghurst, New South Wales, Australia

Genesis Cancer Care Newcastle

Gateshead, New South Wales, Australia

Gosford Hospital

Gosford, New South Wales, Australia

Liverpool Hospital

Liverpool, New South Wales, Australia

Calvary Mater Newcastle

Newcastle, New South Wales, Australia

Mater Hospital Sydney

North Sydney, New South Wales, Australia

Port Macquarie Base Hospital

Port Macquarie, New South Wales, Australia

Prince of Wales Hospital

Randwick, New South Wales, Australia

Tamworth Rural Referral Hospital

Tamworth, New South Wales, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Wollongong Hospital

Wollongong, New South Wales, Australia

Genesis Cancer Care Wesley

Auchenflower, Queensland, Australia

Cancer Care Service - Bundaberg

Bundaberg, Queensland, Australia

Cancer Care Service - Hervey Bay

Bundaberg, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

GenesisCare Tennyson

Kurralta Park, South Australia, Australia

Ballarat Austin Radiation Oncology Centre

Ballarat, Victoria, Australia

Peter MacCallum Cancer Centre - Bendigo

Bendigo, Victoria, Australia

Peter MacCallum Cancer Centre - Moorabin

Bentleigh East, Victoria, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

Icon Cancer Centre Richmond

East Melbourne, Victoria, Australia

St Vincent's Hospital Melbourne

Fitzroy, Victoria, Australia

GenesisCare Radiation Oncology Centre Frankston

Frankston, Victoria, Australia

University Hospital Geelong

Geelong, Victoria, Australia

Austin Hospital

Heidelberg, Victoria, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Ringwood Radiation Oncology Centre

Ringwood East, Victoria, Australia

Latrobe Regional Hospital

Traralgon, Victoria, Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Hospital Luis Tisne Brousse

Santiago, Santiago Metropolitan, Chile

Centro Oncologico del Norte

Antofagasta, , Chile

Hospital Sotero del Rio

Puente Alto, , Chile

Hospital Barros Luco Trudeau

San Miguel, , Chile

Instituto Nacional del Cancer

Santiago, , Chile

St Luke's Radiation Oncology Network

Dublin, , Ireland

University Hospital Galway

Galway, , Ireland

ASST Ospedale A. Manzoni UOS Oncologia

Lecco, , Italy

Istituto Europeo di Oncologia

Milan, , Italy

Christchurch Hospital

Christchurch, , New Zealand

Waikato Hospital

Hamilton, , New Zealand

Palmerston North Hospital

Palmerston North, , New Zealand

Wellington Hospital

Wellington, , New Zealand

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Universitari Arnoa de Vilanova de Lleida

Lleida, , Spain

Hospital Universitario Virgen de la Macarena

Seville, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hirslanden Clinique des Grangettes

Chêne-Bougeries, , Switzerland

Fondazione Oncologia Lago Maggiore

Locarno, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

Brust-Zentrum AG Zurich

Zurich, , Switzerland

Universitatsspital Zurich

Zurich, , Switzerland

Changhua Christian Hospital

Changhua, , Taiwan

Kaohsiung Medical University Hospital

Kaohsiung City, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Mackay Memorial Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Tri-Service General Hospital

Taipei, , Taiwan

Taipei Medical University Hospital

Taipei, , Taiwan

Chang-Gung Memorial Hospital

Taoyuan District, , Taiwan

Countries

Argentina; Australia; Chile; Ireland; Italy; New Zealand; Spain; Switzerland; Taiwan

Related Links

https://www.breastcancertrials.org.au/home

Breast Cancer Trials (formerly Australia \& New Zealand Breast Cancer Trials Group

Other Identifiers

2016-003527-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ANZ1601/BIG 16-02

Identifier Type: -

Identifier Source: org_study_id