Testing Whether Treating Breast Cancer Metastases With Surgery or High-Dose Radiation Improves Survival

Open to females ages 18 years and up

• A patient cannot be considered eligible for this study unless all of the following conditions are met.
• Pathologically confirmed metastatic breast cancer
• Known estrogen, progesterone, and HER2 status of either primary tumor or metastasis;
  • Note: estrogen, progesterone and HER2 status of metastasis preferred for stratification
• Number of allowable metastases:
  • =< 4 metastases seen on standard imaging within 60 days prior to registration when all metastatic disease is located within the following sites:
    • Peripheral lung
    • Osseous (bone)
    • Spine
    • Central lung
    • Abdominal-pelvic metastases (lymph node/adrenal gland)
    • Liver
    • Mediastinal/cervical lymph node
• All known disease amenable to metastasis-directed therapy with either SBRT or resection
  • Note: Symptomatic bone metastasis are allowed if ablative therapy can be delivered
  • Note: Sites for possible surgical excision include lung, liver, adrenal gland, bone, small intestine, large intestine, ovary, and amenable nodal disease sites
  • Note: Surgical stabilization is allowed for a metastasis if it is followed by conventionally fractionated external beam radiotherapy
• Maximum diameter of individual metastasis in any dimension =< 5 cm
• There are no restrictions on distance between the metastases
• Patients must be registered within 365 days of the initial metastatic breast cancer diagnosis; first-line standard systemic therapy (chemotherapy, anti-endocrine therapy, anti-HER2, or other standard targeted therapy) for metastatic breast cancer must be given or planned to be given; if given before study entry, it cannot have exceeded a duration of 12 months at the time of registration (Note: sequencing of ablative therapy [surgery or SBRT] relative to systemic therapy, for patients randomized to Arm 2, is at the discretion of the treating physician)
• The primary tumor site must be controlled prior to registration
  • For those who present with synchronous primary and oligometastatic disease, primary must be controlled prior to registration
  • The definition of control is definitive surgery by excision or mastectomy (+/- radiotherapy) per institution preference For those who present with local recurrence and oligometastatic disease, local recurrence must be controlled prior to registration
  • The definition of control is definitive surgery by excision or mastectomy (+/- radiotherapy) per institution preference
• Appropriate stage for study entry based on the following diagnostic workup:
  • History/physical examination within 60 days prior to registration
  • Clinical grade computed tomography (CT) scans of the chest, abdomen, and pelvis with radionuclide bone scan OR whole body positron emission tomography (PET)/CT within 60 days prior to study registration
• Zubrod performance status =< 2 within 60 days prior to registration
• Blood cell count (CBC)/differential obtained within 60 days prior to registration on study
• Absolute neutrophil count (ANC) >= 500 cells/mm³
• Platelets >= 50,000 cells/mm³
• Hemoglobin >= 8.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
• For females of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to study registration
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

• Patients with any of the following conditions are NOT eligible for this study.
• Pathologic evidence of active primary disease or local/regional breast tumor recurrence at the time of registration;
• Co-existing or prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 3 years; previous RT dose, date, fraction size, must be reported
• Metastases with indistinct borders making targeting not feasible
  • Note: A potential issue with bone metastases is that they often are not discrete; since many patients on this protocol will have bone metastases, this will be an important issue; theoretically, Houndsfield units might provide an appropriate measure; however, a sclerotic lesion against dense cortical bone will not have a sharp demarcation based on Houndsfield units (HU); therefore, we acknowledge that such determinations will pose a challenge and thus the physician's judgment will be required
• Prior palliative radiation treatment for metastatic disease to be treated on the protocol (including radiopharmaceuticals)
• Metastases located within 3 cm of the previously irradiated structures:
  • Spinal cord previously irradiated to > 40 Gy (delivered in =< 3 Gy/fraction)
  • Brachial plexus previously irradiated to > 50 Gy (delivered in =< 3 Gy/fraction)
  • Small intestine, large intestine, or stomach previously irradiated to > 45 Gy (delivered in =< 3 Gy/fraction)
  • Brainstem previously irradiated to > 50 Gy (delivered in =< 3 Gy/fraction)
  • Whole lung previously irradiated with prior percent volume receiving greater than or equal to 20 Gy (V20Gy)> 30% (delivered in =< 3 Gy/fraction)
  • Primary tumor irradiated with SBRT
  • Metastasis irradiated with SBRT
• Brain metastases
• Exudative, bloody, or cytological proven malignant effusions
• Severe, active co-morbidity defined as follows:
  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
  • Transmural myocardial infarction within the last 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
• Pregnancy; lactating females must cease expression of milk prior to signing consent to be eligible
• Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a cluster of differentiation 4 (CD4) count >= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol