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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,167
Omission of radiation therapy (adjuvant endocrine therapy only).
Local recurrence rate after breast conserving surgery
The time from randomisation to the date of local recurrence (LR) as a site of first recurrence.
Time frame: 10 years
Local-regional recurrence-free interval (LRRFI)
Time from randomisation to the date of local or regional recurrence as a site of first recurrence.
Time frame: 10 years
Distant recurrence-free interval (DRFI)
Time from randomisation to the date of distant recurrence, regardless of occurrence of any intervening local or regional recurrence, contralateral breast cancer or second (non-breast) primary invasive cancer.
Time frame: 10 years
Disease free survival including DCIS (DFS-DCIS)
Time from randomisation to date of first evidence of local (invasive breast carcinoma or DCIS), regional or distanct recurrence; contralateral breast cancer (invasive breast carcinoma or DCIS); second (non-breast) primary invasive cancer; or death.
Time frame: 10 years
Invasive disease free survival (iDFS)
Time from randomisation to date of first evidence of local (invasive breast carcinoma), regional or distanct recurrence; contralateral breast cancer (invasive breast carcinoma); second (non-breast) primary invasive cancer; or death.
Time frame: 10 years
Recurrence-free interval
Time from randomisation to the date of local, regional or distant recurrence as a site of first recurrence.
Time frame: 10 years
Overall survival (OS)
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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
...and 58 more locations
Time from randomisation to date of death from any cause.
Time frame: 10 years
Salvage RT or mastectomy rate
Time from randomisation to the receipt of salvage RT or mastectomy, individually and in combination (one or the other) as a composite endpoint.
Time frame: 10 years
Adverse events for patients
Adverse events during treatment (up to 5 years of endocrine therapy) assessed using NCI CTCAE v4.0.
Time frame: 5 years
Assessment of the impact of endocrine therapy
FACT-ES measure of endocrine symptoms.
Time frame: 5 years