Proton Radiation for Stage II/III Breast Cancer

The proposed Phase II study is seeking to build clinical data as a continuation of the
original dosimetric analysis published by Ares et al. performed at Paul-Scherrer Institute
(PSI). That comparison demonstrated a benefit form proton planning for patients with
non-metastatic breast cancer requiring complex, loco-regional, postoperative radiotherapy.1
The advantages of PT were improved target coverage compared to standard photon irradiation
and reduced dose to heart, lungs and contralateral breast.

The study goal is to demonstrate a "meaningful benefit" of proton therapy for women with
loco-regionally advanced breast cancer. The main clinical endpoints of this trial are the
reduction of cardiac morbidity and mortality (coronary artery disease, myocardial infarction,
cardiac insufficiency) and the reduction of contralateral, second breast cancer. Both adverse
events are presently associated with external beam photon therapy. Both goals require
longitudinal follow-up of minimum 5-10 years. Despite the logistical challenges of long term
follow-up, the effort is needed in view of the compelling preclinical evidence of dose
avoidance or even absence of radiation dose to heart and contralateral breast uniquely
accomplishable by protons only.

Inclusion Criteria:

1. 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.

2. Must be > = 18 years of age.

3. Must have a life expectancy of at least 10 years based on age and comorbidities but
excluding diagnosis of breast cancer.

4. Must have pathology proven breast cancer. Pathology must be invasive ductal or lobular

5. Must meet stage II - III group criteria per AJCC Staging manual 7th edition.

6. Must have had surgical treatment of the breast - either mastectomy or breast
preserving surgery, such as lumpectomy. Re-excision of surgical margins is permitted.

7. Note: Multicentric breast cancer and Paget's disease of the nipple are permitted.

Exclusion Criteria:

1. Weight over 410 pounds.

2. Non-epithelial breast malignancies such as sarcoma or lymphoma.

3. Surgical margins that cannot be microscopically assessed or are positive at pathologic
evaluation. (If surgical margins are rendered free of disease by re-excision, the
patient is eligible).

4. Breast size exceeding the technical limitation of daily set-up reproducibility. This
may be center-specific and will be assessed at the discretion of the treating center.

5. Women with post-surgical temporary breast expanders will require individual
assessment. Depending on the manufacturing product and other treatment
planning-specific details the patient may be eligible or may be deemed ineligible, as
determined by treating investigator.

6. Prior history of breast cancer.

7. Prior radiation to the breast or thorax.

8. Collagen vascular disease, specifically dermatomyositis with a CPK level above normal
or with an active skin rash, systemic lupus erythematosis, or scleroderma.

9. Pregnancy or lactation at the time of proposed study entry. Women of reproductive
potential must agree to use an effective non-hormonal method of contraception during
therapy such as an intrauterine device or condom with spermicide. (Note: Women of
childbearing potential must have a negative serum pregnancy test within 3 weeks of
study registration).

10. Psychiatric or addictive disorders or other conditions that, in the opinion of the
investigator, would preclude the patient from meeting the study requirements.

11. Prior history of non-breast malignancies unless they have been disease free for 5 or
more years and are deemed by their physician to be at low risk for recurrence.
Further, patients who have the following cancers treated within the prior 5 years are
permitted: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma
in situ, basal cell or squamous cell carcinoma of the skin.