Phase II Protocol of Proton Therapy for Partial Breast Irradiation in Early Stage Breast Cancer

Inclusion Criteria:

• Must sign study-specific, IRB approved informed consent form prior to study entry.Note consent by legally authorized representative is not allowed for this trial.

• Must be female.

• Must be > = 50 years of age.

• Must have a life expectancy of at least 5 years based on age and co-morbidities.

• Must have pathology proven invasive ductal carcinoma (lobular is not allowed) and/orductal carcinoma in situ (DCIS).

• One of the following criteria must be met: (a) Tumors that are microscopicallymultifocal must be 3.0 cm or less in total aggregate size and encompassed within asingle scar (b) Patient does not have microscopically multifocal tumor.

• For tumors that are invasive, if in the presence of extensive intraductal component (EIC), the entire pathologic tumor size (including both the intraductal and invasivecomponent) must be 3.0 cm or less.

• Must be Stage 0, I, II (Tis, T1, or T2, N0, M0 per AJCC criteria 7th and/or 8thEd.). If stage II, the tumor size must be < = 3.0 cm. A patient with invasivehistology must have nodal stage pN0 by H&E stains on sentinel node biopsy oraxillary lymph node dissection.

• Must have ER positive disease with ER/PR report available.

• For tumors that are invasive, HER2 must be performed (positive or negative isacceptable).

• Must have a lumpectomy performed, with documented negative surgical margins by 0.2cm or more. If re-excision results in negative surgical margins 0.2 cm or more,patient is eligible.

• If image guidance with daily cone beam CT with direct physician visual assessment isused for treatment positioning, the presence of markers or clips in the surgical bedis recommended but not required. If cone beam CT imaging will NOT be used for imageguidance, then the patient must be prepared to have 2 fiducial markers minimum, 3preferred, placed prior to treatment (if not previously done).

• If markers or clips were placed at the time of surgery, patient must be able tostart treatment within 12 weeks after lumpectomy or re-excision for adequatemargins.

• If markers were not placed at the time of surgery and are needed, patient musthave markers placed within 6 weeks after surgery.

• If systemic chemotherapy was given, patient must have had clips or markersplaced at the time of surgery (if they are needed) and patient must havesimulation scans within 6 weeks of the completion of the chemotherapy.

• Must be able to start treatment within 12 weeks of surgery or 8 weeks offinalization of chemotherapy.

Exclusion Criteria:

• Previous history of ipsilateral invasive breast cancer or DCIS.

• Any clinical or radiographically suspicious nodes, unless biopsy proven benign.

• Non-epithelial malignancies such as sarcoma or lymphoma.

• Suspicious residual microcalcifications on mammography of either breast, unlessnegative for malignancy on pathology.

• Multicentric or bilateral disease unless biopsy of the clinical abnormalities areperformed and result is negative.

• Lymphovascular space invasion (LVSI) on pathology specimen.

• Any previously treated breast carcinoma or synchronous breast carcinoma inipsilateral breast.

• Prior radiation therapy to the ipsilateral breast or thorax.

• Paget's disease of the nipple.

• Histologic examination showing invasive lobular histology.

• Skin involvement.

• Breasts technically unsatisfactory for radiation treatment upon the discretion ofthe treating physician.

• Significant infection or other co-existing medical condition that would precludeprotocol therapy such as pregnancy, HIV/AIDS or collagen vascular diseasesspecifically systemic lupus erythematosus, scleroderma, or dermatomyositis.

• Known BRCA 1 or BRCA 2 mutation.

• Pregnant or lactating.