The goal of the project is to identify a molecular signature of tumor stroma from "normal" adjacent breast tissue obtained prospectively at the time of breast conserving surgery before and after receiving intraoperative radiation therapy (IORT) in subjects that have luminal A and triple negative breast cancer. IORT is considered as being standard of care.

There is evidence that the normal tissue around a tumor plays a role in determining how the tumor behaves, including how it will respond to treatments and how likely it is to recur. In breast cancer, radiation is used to decrease the chance of recurrence in the area where the tumor is removed. This risk of recurrence varies between different types of breast cancer. The investigators seek to study the proteins produced in normal tissue surrounding breast tumors. The tissue will be taken from women who are receiving radiation to the breast at the time of their surgery (known as intraoperative radiation), one specimen taken before radiation and one after. A new process will be used to stabilize the tissue rapidly and allow the proteins to be identified before they break down. This will allow us to identify differences in the proteins produced by cells before and after radiation and between two types of breast cancers, luminal A (less likely to recur) and triple negative (more likely to recur). Identifying these differences in proteins may allow them to be used in the future as markers to predict the likelihood of tumors recurring.

Inclusion Criteria:

• Female, age greater than or equal to 40
• Core biopsy proven invasive breast carcinoma or ductal carcinoma in situ (DCIS), all subtypes excluding invasive lobular carcinoma due to increased risk for multifocal disease
• Human epidermal growth factor receptor 2 (HER2) negative regardless of hormone receptor status
• Clinically less than or equal to 3cm unifocal lesion
• Clinically node negative
• Must have diagnostic mammogram performed within last 6 months
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) less than or equal to 1
• Appropriate renal, liver, and hematologic lab values
• Ability to give informed consent

Exclusion Criteria:

• Multifocal disease
• Clinically N1 disease at diagnosis
• Invasive lobular carcinoma
• Metastatic disease
• Patients for whom RT would be contraindicated (e.g., connective tissue disorder or prior ipsilateral breast radiation)
• Patients with known BRCA1/2 mutations
• Pregnant or nursing

Subjects will be recruited from the outpatient Breast Surgery and Radiation Oncology Clinics of Columbia University