Regional Radiotherapy in Biomarker Low-Risk Node Positive and T3N0 Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to compare the effects on low risk breast cancer receiving usual care that includes regional radiation therapy, with receiving no regional radiation therapy. Researchers want to see if not giving this type of radiation treatment works as well at preventing breast cancer from coming back.

Detailed Description
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Women with node positive breast cancer normally will receive endocrine therapy and some may receive chemotherapy to help prevent the cancer from coming back. Many women will also receive radiotherapy to the whole breast/chest area and the surrounding lymph glands (called regional radiotherapy). No one really knows whether patients with low risk breast cancer need to receive regional radiotherapy. Some women may be getting regional radiotherapy who do not need it. These women may be exposed to the side effects of their treatment without benefit.

Official Title
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TAILOR RT: A Randomized Trial of Regional Radiotherapy in Biomarker Low-Risk Node Positive and T3N0 Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Radiation: Radiation
* Other: No Radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be women with newly diagnosed histologically proven invasive carcinoma of the breast with no evidence of metastases, staged as per site standard of care. Patients must have been treated by BCS or mastectomy with clear margins of excision. Post-mastectomy positive margins for invasive disease and/or DCIS is not allowed. Multifocal disease (i.e. the presence of two or more foci or breast cancer within the same breast quadrant) and multicentric disease (i.e. the presence of two or more foci of breast cancer in different quadrants of the same breast) are allowed. Patients with T3N0 disease are eligible. Patients with disease limited to nodal micrometastases are eligible Patients with nodal macrometastases (>2mm) treated by axillary dissection must have 1-3 positive axillary nodes (macrometastases, > 2 mm). Patients treated by mastectomy and SLNB alone must have only 1-2 positive axillary nodes (macrometastases, > 2 mm). Patients must be ER ≥ 1% and HER2 negative on local testing Patients must have an Oncotype DX recurrence score ≤25 obtained from testing of breast tumour tissue from a core biopsy or from the surgical specimen. Patient must consent to provision of, and investigator(s) must agree to submit to the CCTG Central Tumour Bank, a representative formalin fixed paraffin block of tumour tissue in order that the specific correlative marker assays described in the protocol may be conducted Patient must consent to provision of samples of blood in order that the specific correlative marker assays described in the protocol may be conducted. Patients must have had endocrine therapy initiated or planned for ≥ 5 years. Premenopausal women will receive ovarian ablation plus aromatase inhibitor therapy or tamoxifen if adjuvant chemotherapy was not administered. For all patients, endocrine therapy can be given concurrently or following RT. Patients may or may not have had adjuvant chemotherapy. RT must commence within 16 weeks of definitive surgery if the patient is not treated with chemotherapy. If adjuvant chemotherapy is given, RT must begin within 12 weeks after the last dose. (Note: adjuvant chemotherapy may be ongoing at the time of randomization). Definitive surgery is defined as the last breast cancer-related surgery. Patient's ECOG performance status must be 0, 1 or 2. Patient's age must be ≥ 35 years. For the first 736 eligible English or French-speaking subjects who have agreed to optional questionnaire completion: Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life, health utilities and lost productivity questionnaires in either English or French (note: enrollment completed 2022Aug02) Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up. In accordance with CCTG policy, protocol treatment is to begin within 6 weeks of patient randomization. Women of childbearing potential must have agreed to use an effective contraceptive method. A woman is considered to be of childbearing potential if she has had menses at any time in the preceding 12 consecutive months. Exclusion Criteria: Patients with nodal disease limited to isolated tumour cells (pN0i+ < 0.2 mm). Patients with pT3N1 and pT4 disease (Note: patients with T3N0 are eligible). Any prior history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated with radiation therapy. (Patients with synchronous or previous ipsilateral LCIS are eligible.) Synchronous or previous contralateral invasive breast cancer. (Patients with contralateral DCIS are eligible unless previously treated with radiation.) History of non-breast malignancies except adequately treated non-melanoma skin cancers, in situ cancers treated by local excision or other cancers curatively treated with no evidence of disease for ≥ 5 years. Patients who are pregnant. Patients that have had prior ipsilateral chestwall/thoracic radiation. Patients treated with chemo or endocrine therapy administered in the neoadjuvant setting for breast cancer. Endocrine therapy exposure 12 weeks or less prior to surgery is permitted. Patients with serious non-malignant disease (e.g. cardiovascular, scleroderma etc.) which would preclude RT. Patients with any serious active or co-morbid medical conditions, laboratory abnormality, psychiatric illness, active or uncontrolled infections, or serious illnesses or medical conditions that would prevent the patient from participating or to be managed according to the protocol (according to investigator's decision).

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: No Regional Radiotherapy<br>A. Whole Breast Irradiation (WBI) following BCS or; B. No Radiotherapy (RT) following mastectomy | Radiation: Radiation<br>* Radiotherapy given<br>Other: No Radiation<br>* No radiotherapy given<br>|
| Active Comparator: Regional Radiotherapy<br>A. WBI plus RT to the regional nodes (supraclavicular, non-dissected axillary, and internal mammary) following BCS or; B. RT to the chestwall and regional nodes (supraclavicular, non-dissected axillary, and internal mammary) following mastectomy | Radiation: Radiation<br>* Radiotherapy given<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| compare the breast cancer recurrence-free interval (BCRFI) between patients that received regional RT or not | Defined as time from randomization to time of invasive recurrent disease in the ipsilateral chestwall, breast, regional nodes, distant sites or death due to BC. | 9.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the invasive disease-free survival between patients that received regional RT or not. | Defined as time from randomization to time of invasive recurrent disease in the ipsilateral chestwall, breast, regional nodes, distant sites or death due to BC | 9.5 years | 
| Compare the breast cancer mortality between patients that received regional RT or not. | Defined as death due to BC | 9.5 years | 
| Compare the overall survival (OS) between patients that received regional RT or not | Defined as the time from randomization to the time of death from any cause | 9.5 years | 
| Compare the locoregional recurrence-free interval (LRRFI) between patients that received regional RT or not. | Defined as time from randomization to time of invasive recurrent disease in the ipsilateral chestwall, breast or regional nodes, or death to due to BC | 9.5 years | 
| Compare the distant recurrence-free interval (DRFI) between patients that received regional RT or not. | Defined as time from randomization to time of invasive recurrent disease in distant sites or death due to BC | 9.5 years | 
| Number and severity of adverse events using the current CTCAE version 4 |  | 9.5 years | 
| Compare arm volume and mobility measurements between patients that received regional RT or not | A Fisher's Exact Test will be used to compare lymphedema and arm abduction deficit between two arms. Defined as a difference in arm abduction of 10% or greater in the comparison of the ipsilateral to the contralateral arm. | 9.5 years | 
| Compare patient-reported outcomes (PROs) and the quality of life (QOL) between patients that received regional RT or not | using the NSABP Questionnaire for patients treated by BCS or mastectomy. | 9.5 years | 
| Compare the quality of life (QOL) between patients that received regional RT or not | Overall QOL (EORTC QLQ-C30) will be compared between the two treatment groups using a similar approach. | 9.5 years | 
| Compare the cost-effectiveness between patients that received regional RT or not | Costs will be expressed in $US and $CAN base currencies based on the final year of the study. An average cost per study subject by treatment arm for an overall mean cost per study arm will be generated | 9.5 years | 
| Compare the quality of life (QOL) between patients that received regional RT or not | breast symptoms (NSABP B32 Questionnaire) will be compared between the two treatment groups using a similar approach. | 9.5 years | 
| Compare the quality of life (QOL) between patients that received regional RT or not | skin symptoms and fatigue (EORTC QLQ-BR23) will be compared between the two treatment groups using a similar approach. | 9.5 years |