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

Current standard of care for early stage breast cancer is mastectomy or breast conserving
therapy with whole breast irradiation following lumpectomy. However, studies of breast cancer
recurrence have demonstrated the majority of tumors to recur in or adjacent to the original
tumor site. The question has thus been raised as to whether radiation to the whole breast is
necessary or justified. Limiting radiation to the area of the original tumor may reduce acute
and long-term skin and organ toxicities while making radiation therapy more convenient and
less expensive. Several clinical trials are underway comparing partial breast irradiation
(PBI) to whole breast irradiation. Numerous centers are offering partial breast irradiation
outside of clinical trials as well, despite the lack of long-term safety and efficacy data on
PBI.

Available PBI methods include brachytherapy, in which catheters or balloons are surgically
inserted to deliver radiation therapy to the lumpectomy cavity, and conventional external
beam radiation therapy, or EBRT. External beam photon therapy is attractive for its
non-invasive nature and ability to deliver a more homogenous dose distribution compared to
brachytherapy, however it also delivers a greater radiation dose to surrounding normal breast
tissue.Proton therapy has the capacity to provide the same advantages as photon EBRT while
minimizing dose to normal surrounding tissue. Clinical data on PBI with protons is minimal,
however, leaving many questions unanswered. The impetus behind this protocol is to address
these gaps by further investigating the feasibility, safety, and efficacy of proton therapy
for partial breast irradiation.

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/or
ductal carcinoma in situ (DCIS).

- One of the following criteria must be met: (a) Tumors that are microscopically
multifocal must be 3.0 cm or less in total aggregate size and encompassed within a
single 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 invasive
component) 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 8th Ed.).
If stage II, the tumor size must be < = 3.0 cm. A patient with invasive histology must
have nodal stage pN0 by H&E stains on sentinel node biopsy or axillary 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 is
acceptable).

- Must have a lumpectomy performed, with documented negative surgical margins by 0.2 cm
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 is
used for treatment positioning, the presence of markers or clips in the surgical bed
is recommended but not required. If cone beam CT imaging will NOT be used for image
guidance, then the patient must be prepared to have 2 fiducial markers minimum, 3
preferred, placed prior to treatment (if not previously done).

- If markers or clips were placed at the time of surgery, patient must be able to
start treatment within 12 weeks after lumpectomy or re-excision for adequate
margins.

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

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

- Must be able to start treatment within 12 weeks of surgery or 8 weeks of finalization
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, unless
negative for malignancy on pathology.

- Multicentric or bilateral disease unless biopsy of the clinical abnormalities are
performed and result is negative.

- Lymphovascular space invasion (LVSI) on pathology specimen.

- Any previously treated breast carcinoma or synchronous breast carcinoma in ipsilateral
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 of the
treating physician.

- Significant infection or other co-existing medical condition that would preclude
protocol therapy such as pregnancy, HIV/AIDS or collagen vascular diseases
specifically systemic lupus erythematosus, scleroderma, or dermatomyositis.

- Known BRCA 1 or BRCA 2 mutation.

- Pregnant or lactating.