Partial Breast Versus no Irradiation for Women With Early Breast Cancer

Study Overview
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Brief Summary
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All early breast cancer patients are offered adjuvant breast radiation therapy (RT) after breast conserving surgery for an early breast cancer. Breast cancer is heterogeneous, and selected patients have a very low gain from RT, whilst they still have risk of acute and late side effects from RT. This trial will try identify selection criteria for low risk breast cancer patients who can safely omit adjuvant RT without unacceptable high risk of local failure.

Detailed Description
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International standard of therapy is to provide adjuvant breast radiation therapy (RT) after breast conserving surgery for an early breast cancer to lower the risk of local and distant failures. However, breast cancer is a heterogeneous disease, and the gain from RT in selected low risk patients is low. RT may cause acute and late side effects, and some of these may be serious to the patient. Therefore, there is a need to tailor RT utilization to the individual recurrence risk and try identify patients who are unlikely to gain much risk reduction from RT, because those patients can then omit RT and thereby avoid late effects and over-treatment. At the present time there is no consensus as to define the selection criteria for patients who may omit RT. Based on early results from the randomized DBCG RT PBI trial, external beam 40 Gy/15 fr partial breast irradiation (PBI) has been standard in Denmark since April 2016 for selected low risk breast cancer patients. Based on results from the UK IMPORT LOW trial, the 5 yr local recurrence risk using this technique for PBI is 0.5%, whilst 2% for developing a new contralateral breast cancer. This trial will investigate if PBI can safely be omitted in selected low risk breast cancer patients without causing unacceptable high risk of local failure.

Official Title
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The DBCG RT Natural Trial: Partial Breast Versus no Irradiation for Women >=60 Years Operated With Breast Conservation for an Early Breast Cancer: a Clinically Controlled Randomized Phase III Trial

Conditions
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Local Neoplasm Recurrence, Distantly Metastatic Malignant Neoplasm, Death, Fibrosis Breast, Depigmentation/Hyperpigmentation of Skin, Telangiectasia, Scar, Pain, PROMs

Intervention / Treatment
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* Radiation: No partial breast irradiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patient >=60 years Primary tumour characteristics by conventional histopathology unilateral and unifocal non-lobular histology grade 1-2 maximum microscopic size <=20mm node negative determined by sentinel node or axillary lymph node dissection estrogen receptor >=10% positive HER2 negative (by IHC and/or in situ hybridization) resection margin >=2 mm for invasive carcinoma and any ductal carcinoma in situ associated with the cancer Surgical type is breast conservation Performance status ECOG 0-2 No evidence of distant metastasis Exclusion Criteria: multifocal or multicentric invasive carcinoma or ductal carcinoma in situ evidence of clinical or pathological T4 breast cancer grade 3 malignancy previous breast cancer or DCIS irrespective of disease-free interval previous radiation therapy to the breast or thorax, previous neoplasm within 5 years except carcinoma in situ of the cervix, endometrium or coli, melanoma in situ. comorbidity precluding the patient from radiation therapy (e.g. cardiovascular or pulmonary disease, scleroderma, systemic lupus erythematosus). mental/psychiatric disorder which precludes the patient from understanding the randomization and the follow up. documented hereditary breast cancer or with high genetic risk of breast cancer life expectancy <10 years

Ages Eligible for Study
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Minimum Age: 60 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
Interventional Model Description: Clinically controlled randomized trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Partial breast irradiation<br>External beam irradiation 40 Gy / 15 fractions, 5 fractions per week, 3 weeks | Radiation: No partial breast irradiation<br>* Omission of radiation therapy<br>|
| No Intervention: No partial breast irradiation<br>No radiation therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive local recurrence | Invasive local recurrence | 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regional nodes recurrence | Invasive recurrence in regional nodes of the treated breast | 10 years | 
| Distant failure | Invasive recurrence from the breast cancer outside the loco-regional area | 10 years | 
| Death | Death and cause of death | 10 years |