A Randomised Phase III Trial of Adjuvant Radiation Therapy Versus Observation Following Breast Conserving Surgery and Endocrine Therapy in Patients With Molecularly Characterised Luminal A Early Breast Cancer
Overview
- Phase
- N/A
- Intervention
- Not specified
- Conditions
- Early Stage Breast Carcinoma
- Sponsor
- Breast Cancer Trials, Australia and New Zealand
- Enrollment
- 1167
- Locations
- 68
- Primary Endpoint
- Local recurrence rate after breast conserving surgery
- Status
- Active, Not Recruiting
- Last Updated
- 7 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •for registration in the study:
- •Female patients aged ≥ 50 years of any menopausal status.
- •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.
- •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.
- •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).
Exclusion Criteria
- •Any one of the following is regarded as a criterion for exclusion from the study:
- •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
- •Contra-indication or unwillingness to have adjuvant endocrine therapy.
- •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.
- •Treated with neoadjuvant endocrine therapy, chemotherapy or biologic therapy prior to breast cancer surgery.
Outcomes
Primary Outcomes
Local recurrence rate after breast conserving surgery
Time Frame: 10 years
The time from randomisation to the date of local recurrence (LR) as a site of first recurrence.
Secondary Outcomes
- Disease free survival including DCIS (DFS-DCIS)(10 years)
- Local-regional recurrence-free interval (LRRFI)(10 years)
- Invasive disease free survival (iDFS)(10 years)
- Recurrence-free interval(10 years)
- Overall survival (OS)(10 years)
- Distant recurrence-free interval (DRFI)(10 years)
- Salvage RT or mastectomy rate(10 years)
- Adverse events for patients(5 years)
- Assessment of the impact of endocrine therapy(5 years)