Focused Ultrasound with Low-Dose Gemcitabine to Increase Immune Control in Patients with Stage I-III Breast Cancer

Inclusion Criteria

• Patients must have histologically confirmed breast cancer * Newly diagnosed patients must have stage 1-3 disease and be appropriate surgical candidates for complete resection * Recurrent disease patients must have disease localized to the breast, chest wall or axilla and must be surgical candidates for complete resection of recurrent disease
• If genomic profiling is performed, then the results must indicate that the cancer is high-risk
• Any receptor status may be eligible (estrogen receptor, progesterone receptor, HER2 receptor)
• Patients must have a lesion in the breast/chest wall/axilla that is accessible to FUS ablation * The chest wall is defined per the National Cancer Institute at the National Institutes of Health (NCI) as: the skin, fat, muscles, bones, and other tissues that form a protective structure around vital organs in the area between the neck and the abdomen, including the heart, major blood vessels, lungs, and liver. The bones in the chest wall include the ribs, sternum (breastbone), and spine. The chest wall also helps support breathing and movement of the upper arms and shoulders * Accessible is defined as the following: ** A targetable portion of the tumor must be >= 5 mm from the skin ** The rib cage should not be in the prefocal ultrasound path or behind the target area of the lesion (minimum distance from the posterior aspect of the target area to rib cage must be at least 10 mm)
• Willing and able to provide written consent for the trial
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, >= 18 years
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Absolute neutrophil count (ANC) >= 1000/mm^3
• Platelets >= 100,000/mm^3
• Hemoglobin >= 9 g/dL
• Serum creatinine =< 1.5 x upper limit of normal (ULN)
• Bilirubin =< 1.5 x ULN (except in patients with Gilbert's disease, where bilirubin to 4 x ULN is allowed)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
• Alkaline phosphatase =< 2.5 x ULN
• Agreement to adhere to Lifestyle Considerations throughout study duration

Exclusion Criteria

• Received other treatment (standard or investigational) for their current breast cancer
• Pregnant or lactating
• Diagnosis of immunodeficiency or receiving systemic steroid therapy within 7 days prior to enrollment with the following exceptions: * In patients with adrenal or pituitary insufficiency replacement steroid doses are allowed; however, daily doses of 10 mg or more of prednisone (or equivalent) per day administered parenterally or orally are not allowed in patients with normal adrenal and pituitary function * Inhaled steroids (e.g.: Advair, Flovent, Azmacort) are permitted at low doses (less than 500 mcg fluticasone per day, or equivalent) * Topical, nasal, and intra-articular corticosteroids are acceptable
• Known allergic reactions to gemcitabine
• Breast implant on the side of the body that will receive HIFU application
• Known history of human immunodeficiency virus (HIV) (Patients with HIV will be excluded because immunotherapy may impact the T cell profiling as part of the biologic correlates and the natural history of the disease)
• Known active hepatitis B virus or hepatitis C virus
• Any other malignancy with the exception of: basal cell carcinoma of the skin or squamous cell carcinoma of the skin that is undergoing potentially curative therapy, ductal carcinoma in situ (DCIS), or in situ cervical cancer
• Active infection requiring other systemic therapy
• Participants in whom there is a medical contraindication or potential problem in complying with the requirements of the protocol in the opinion of the investigator
• Any condition(s) or diagnosis, both physical or psychological, or physical exam finding that precludes participation