This study assesses if metastasis-directed radiation therapy (Stereotactic body radiation therapy - SBRT) can delay a change in systemic therapy, and if circulating tumor cells in the bloodstream can help guide treatment options in metastatic breast cancer patients with progressive disease

Inclusion Criteria:

• Age ≥ 18 years.

• Histological confirmation of primary breast cancer.

• Patients with metastatic breast cancer and at least 12 months of clinical response to first-line systemic therapy, with the subsequent development of 1-3 extracranial sites of oligoprogressive disease, and who plan for the continuation of the current systemic therapy.

  • NOTE: patients with de novo metastatic disease and those developed metastatic disease after initially localized disease can both be included.

OR

• Patients with metastatic breast cancer and at least 6 months of clinical response to second-line systemic therapy (or further, e.g., third- or fourth-line), with the subsequent development of 1-3 extracranial sites of oligoprogressive disease.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2.
• Negative urine or serum pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only.
• Ability to complete questionnaire(s) by themselves or with assistance.
• Provide written informed consent.
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
• Willing to provide blood samples for correlative research purposes.
• Receiving radiation therapy as specified in the protocol.

Exclusion Criteria:

• Male patients.

• Nursing or pregnant women.

• Men or women of childbearing potential who are unwilling to employ adequate contraception.

• Patients with triple negative disease (negative for ER, PR, and HER2).

• Active second primary malignancy

• More than 3 extracranial sites of oligoprogressive disease

• Active CNS disease. Patients with asymptomatic and stable, treated CNS lesions (radiation and/or surgery and/or other CNS-directed therapy who have not received corticosteroids for at least 4 weeks) are allowed.

  • Active connective tissue disease that is felt by the treatment team to pose an excess risk of toxicity.

  • Prior radiation that overlaps with the intended treatment volume such that, in the opinion of the patient's Radiation Oncologist, radiotherapy to progressing sites will not be safe.

    • NOTE: patients with some dose overlap with prior radiotherapy that is deemed safe by the patient's Radiation Oncologist can be included in the trial.