Omission of radiation therapy: Omission of radiation therapy (adjuvant endocrine therapy only).
Study 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.
Eligibility
Sex
FEMALE
Min age
50 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria: for registration in the study:
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.
Primary outcome measure(s)
Local recurrence rate after breast conserving surgery — 10 years The time from randomisation to the date of local recurrence (LR) as a site of first recurrence.
Trial sites (68)
Facility
City
Region
Status
Sanatorio Britanico Rosariio
Rosario
Santa Fe Province
Instituto de Oncologia de Rosario
Santa Fe
Argentina
Clinica Viedma
Sarmiento
Argentina
The Canberra Hospital
Canberra
Australian Capital Territory
Macarthur Cancer Therapy Centre
Campbelltown
New South Wales
The Chris O'Brien Lifehouse
Camperdown
New South Wales
St Vincent's Hospital, Sydney
Darlinghurst
New South Wales
Genesis Cancer Care Newcastle
Gateshead
New South Wales
Gosford Hospital
Gosford
New South Wales
Liverpool Hospital
Liverpool
New South Wales
Calvary Mater Newcastle
Newcastle
New South Wales
Mater Hospital Sydney
North Sydney
New South Wales
Port Macquarie Base Hospital
Port Macquarie
New South Wales
Prince of Wales Hospital
Randwick
New South Wales
Tamworth Rural Referral Hospital
Tamworth
New South Wales
Westmead Hospital
Westmead
New South Wales
Wollongong Hospital
Wollongong
New South Wales
Genesis Cancer Care Wesley
Auchenflower
Queensland
Cancer Care Service - Bundaberg
Bundaberg
Queensland
Cancer Care Service - Hervey Bay
Bundaberg
Queensland
Princess Alexandra Hospital
Woolloongabba
Queensland
GenesisCare Tennyson
Kurralta Park
South Australia
Ballarat Austin Radiation Oncology Centre
Ballarat
Victoria
Peter MacCallum Cancer Centre - Bendigo
Bendigo
Victoria
Peter MacCallum Cancer Centre - Moorabin
Bentleigh East
Victoria
Box Hill Hospital
Box Hill
Victoria
Icon Cancer Centre Richmond
East Melbourne
Victoria
St Vincent's Hospital Melbourne
Fitzroy
Victoria
GenesisCare Radiation Oncology Centre Frankston
Frankston
Victoria
University Hospital Geelong
Geelong
Victoria
Austin Hospital
Heidelberg
Victoria
Peter MacCallum Cancer Centre
Melbourne
Victoria
Ringwood Radiation Oncology Centre
Ringwood East
Victoria
Latrobe Regional Hospital
Traralgon
Victoria
Sir Charles Gairdner Hospital
Nedlands
Western Australia
Hospital Luis Tisne Brousse
Santiago
Santiago Metropolitan
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
+ 28 more sites — see the full list on the official registry below.
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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