Adding Surgery and Radiation to the Usual Treatment for HER2-Positive Breast Cancer That Had Already Spread at Diagnosis

Registry record from ClinicalTrials.gov (NCT07578116). This is a study registration, not published results. Lead sponsor: SWOG Cancer Research Network. Recruitment status: RECRUITING. Phase: PHASE3. Study type: INTERVENTIONAL. Enrollment: 562 participants (ESTIMATED). Conditions: Anatomic Stage IV Breast Cancer AJCC v8, Metastatic HER2-Positive Breast Carcinoma, Oligometastatic Breast Carcinoma. Interventions: PROCEDURE: Biopsy Procedure; PROCEDURE: Biospecimen Collection; PROCEDURE: Breast Conservation Treatment; PROCEDURE: Computed Tomography; DRUG: Cyclin-Dependent Kinase 4 Inhibitor; DRUG: Cyclin-Dependent Kinase 6 Inhibitor; PROCEDURE: Echocardiography Test; DRUG: HER2-targeted Therapy; DRUG: Hormone Therapy; PROCEDURE: Magnetic Resonance Imaging; PROCEDURE: Mammography; BIOLOGICAL: Pertuzumab; PROCEDURE: Positron Emission Tomography; RADIATION: Radiation Boost; RADIATION: Radiation Therapy; RADIATION: Stereotactic Body Radiation Therapy; RADIATION: Stereotactic Radiosurgery; DRUG: Taxane Compound; PROCEDURE: Total Mastectomy; BIOLOGICAL: Trastuzumab; BIOLOGICAL: Trastuzumab Deruxtecan; BIOLOGICAL: Trastuzumab Emtansine; PROCEDURE: Ultrasound Imaging. Primary outcome measures: Overall survival (OS) (Cohort A) , From date of Step 2 registration to date of death, assessed up to 10 years; Progression-free survival (PFS) (Observational Cohort B) , From date of Step 2 registration to date of first documentation of progression or recurrence or death, assessed at 3 and 5 years; Overall survival (Observational Cohort B) , From date of Step 2 registration to date of death, assessed at 3 and 5 years. Brief summary: This phase III trial evaluates the effect of adding locoregional therapy (surgery and radiation) and metastasis-directed stereotactic body radiation therapy (SBRT) to standard systemic therapy following standard HER2-targeted systemic therapy, compared to standard systemic therapy alone, in treating patients with HER2-positive stage IV breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or to a limited number of sites (oligometastatic). The usual approach for patients with (oligo)metastatic HER2-positive breast cancer is systemic drug treatment, which means medicines that travel through the whole body to treat both the breast and any areas where the cancer has spread. There are a number of approved HER2-targeted systemic therapy regimens available to patients. These typically include immunotherapy and/or chemotherapy. Immunotherapy drugs may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Unlike systemic therapy, locoregional therapies like surgery and radiation are focused treatments at the site of disease, delivered with the intent of sparing healthy tissues. Breast surgeries such as breast conserving therapy or total mastectomy are procedures in which the cancerous breast tissue (and healthy breast tissue in the case of total mastectomy) are surgically removed from the body. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. SBRT is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Adding locoregional therapy, as well as metastasis-directed SBRT, to standard systemic therapy may help patients with (oligo)metastatic, HER2-positive stage IV breast cancer live longer overall or before their cancer progresses, and may help more patients achieve no evidence of disease, when compared to standard systemic therapy alone.