EXamining PErsonalised Radiation Therapy for Low-risk Early Breast Cancer

  • STATUS
    Recruiting
  • End date
    Dec 31, 2023
  • participants needed
    1167
  • sponsor
    Breast Cancer Trials, Australia and New Zealand
Updated on 31 August 2020
Investigator
Heath Badger
Primary Contact
Mater Hospital Sydney (5.9 mi away) Contact
+46 other location

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.

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.

Details
Treatment Omission of radiation therapy
Clinical Study IdentifierNCT02889874
SponsorBreast Cancer Trials, Australia and New Zealand
Last Modified on31 August 2020

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Eligibility

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Inclusion Criteria

Is your age greater than or equal to 50 yrs?
Are you female?
Do you have Early Stage Breast Carcinoma?
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)
No evidence of distant metastasis
Eligible for and willing to have adjuvant endocrine therapy
ECOG performance status 0-2
Availability of FFPE tumour block for Prosigna (PAM50) Assay
For randomization to the study, patients must fulfill all of the following criteria
Primary tumour characteristics as assessed by Prosigna (PAM50) Assay
Luminal A intrinsic subtype
ROR score 60
Any one of the following is regarded as a criterion for

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
Prior breast or thoracic RT for any condition
Pre-operative breast imaging evidence of disease aside from the primary carcinoma resected by breast conserving surgery
Concurrent invasive breast carcinoma or ductal carcinoma in situ (synchronous or metachronous)
Prior diagnosis of invasive breast carcinoma or ductal carcinoma in situ in either breast irrespective of disease free interval
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
Significant comorbidity precluding definitive RT for breast cancer (e.g. cardiovascular or pulmonary disease, scleroderma, systemic lupus erythematosus)
Life expectancy <10 years
Documented mutation of BRCA1, BRCA2 or TP53, or at high genetic risk of breast cancer
Pregnant or lactating patients
Inability to be registered to the study 8 weeks after the last surgical procedure for breast cancer
Inability to commence RT (if randomised to receive RT) no later than 12 weeks from the last surgical procedure for breast cancer
Inability to provide written informed consent
Psychiatric, addictive, or any disorder that precludes compliance with protocol requirements
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