The study is being done to determine if stereotactic ablative radiotherapy (SABR) can control tumour growth for patients with metastatic breast cancer.

Secondary objectives will be overall survival, progression-free survival and time to switch of next line of systemic therapy.

Radiation-related adverse events will be assess, with a specific focus on dermatitis, lymphedema and brachial plexopathy.

The exploratory objective is to correlate toxicities and outcomes with peripheral blood biomarkers and circulating tumor DNA to potentially help predict responses in future patients receiving combined therapy.

Purpose:

The purpose of this study is to determine if stereotactic ablative radiotherapy (SABR) can provide effective locoregional control for patients with metastatic breast cancer. As secondary objectives, the investigators will assess the overall survival, progression-free survival and time to switch of next line of systemic therapy. The investigators will also assess radiation-related adverse events using CTCAE v5.0, with a specific focus on dermatitis, lymphedema and brachial plexopathy. Finally, as an exploratory objective, the investigators aim to correlate toxicities and outcomes with peripheral blood biomarkers and circulating tumor DNA to potentially help predict responses in future patients receiving combined therapy.

Primary Objective:

• Assess median, 1-year and 2-year locoregional control

Secondary Objectives:

• Assess median, 1-year and 2-year overall survival
• Assess median, 1-year and 2-year progression-free survival
• Assess median time to systemic therapy switch
• Assess radiation-related adverse events using CTCAE v5.0

Correlative Objectives:

• Correlate outcomes with peripheral blood-derived parameters

Research Design The trial is designed as a single-arm interventional study investigating stage IV breast cancer with persistent or progressive locoregional disease despite the use of standard systemic therapy A retrospective study will be conducted to create a matched cohort to compare locoregional control rates with patients who received conventional fractionated radiotherapy.

Inclusion Criteria:

1. Pathologically confirmed AJCC 7th/8th edition Stage IV invasive ductal carcinoma or invasive lobular carcinoma of the breast.

2. Measurable disease in the breast, suitable to receive radiotherapy.

3. Receiving or planned to receive systemic therapy.

   a. The following should be held for the duration of treatment: cytotoxic chemotherapy, CDK4/6 inhibitors, T-DXd

4. Patients are allowed to have SABR for oligometastatic disease as clinically indicated

5. Age 18 or older

6. ECOG Performance Status 0-2

7. Life expectancy greater than 6 months

8. Able and willing to provide informed consent

9. Able to complete patient reported outcome questionnaires

Exclusion Criteria:

1. Contraindications to radiotherapy, including a history of SLE, systemic scleroderma, IPF, ataxia telangiectasia, pregnancy
2. Previous history of locoregional radiotherapy to the ipsilateral breast