Focused Ultrasound and Gemcitabine in Breast Cancer

Inclusion criteria

• Disease Status

• Patients must have histologically confirmed, newly diagnosed breast cancer, 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 completion 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 focused ultrasound ablation.

Accessible is defined as the following:

• A targetable portion of the tumor must be ≥ 5mm 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).

Participants must have at least one high-risk feature of breast cancer (tumor size and nodal status may be measured by mammogram, MRI, US, CT, or calipers):

• Triple negative breast cancer with Tumor size ≥10mm
• Lymph node involvement by imaging or biopsy (any receptor status, any size)
• Tumor size ≥ 20mm (estrogen receptor positive, HER2 negative)
• Tumor size ≥ 10mm (HER2 receptor positive, any ER status)
• Tumor size ≥ 10mm and Oncotype or Mammaprint high status (estrogen receptor positive, HER2 negative) *If patient has more than one tumor, then the treated tumor must have a high-risk feature (if 2 tumors meet high risk criteria), they may both be treated).

• Willing and able to provide written consent
• 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.
• ECOG performance status of 0-2
• Adequate organ function
• Agreement to adhere to lifestyle considerations throughout the 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 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
• Other malignancy other than 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