Shorter Course Radiation for the Treatment of Breast Cancer That Has Spread to Lymph Nodes

Subjects who join the study will receive a shortened course of radiation treatment that will
last approximately four (4) weeks, instead of the traditional six (6) week course that women
have typically received in this situation. The shorter course subjects will receive is
designed in a way that it is thought to be equivalent to the longer course. This shorter
course has already been shown to be very safe and effective when treating breast cancer in
the breast tissue only. However, because cancer cells were found in the lymph nodes that
drain their breast, subjects require radiation to a larger area of their chest, armpit, and
shoulder than has been completely tested with this experimental dose.

Inclusion Criteria:

1. Adult women (≥18 years old) with breast cancer who have undergone surgery for their
primary breast tumor (either lumpectomy or mastectomy +/- reconstruction) and are
confirmed to have involved lymph nodes on surgical pathology.

2. Patient who have undergone either a total mastectomy or a lumpectomy are eligible.
Acceptable procedures for assessment of axillary nodal status at the time of surgery
include:

- axillary node dissection;

- sentinel node biopsy alone; or

- sentinel node biopsy followed by axillary node dissection.

3. Eligible women include (American Joint Committee on Cancer) AJCC 7th ed. Stage cN0 or
cN1 subsequently staged after surgery as Stage pIB (N1mic), pIIA, pIIB, pIIIA, or
pIIIB: note that ypN0 will also be eligible if pathologic confirmation of nodal
involvement was documented prior to neoadjuvant chemotherapy and the patient was found
to be node negative at the time of surgery. Note that women less than 50 years of age,
women who received chemotherapy, patients staged as pN0 (i+ or mol+), and
large-breasted women are eligible for enrollment.

4. The patient must have recovered from surgery with the incision completely healed and
no signs of infection. If adjuvant chemotherapy was administered, chemotherapy-related
toxicity that may interfere with delivery of radiation therapy should have resolved.
The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status
of 0 or 1 (KPS >70%).

5. The interval between the last surgery for breast cancer (including re-excision of
margins) and randomization must be no more than 180 days if chemotherapy is not
delivered adjuvantly. If adjuvant chemotherapy was administered, the interval between
the last chemotherapy treatment and randomization must be no more than 180 days.

6. Before the patient is enrolled, the consent form, including any addenda, must be
signed and dated by the patient and the person who explains the study to that patient.

Exclusion Criteria:

1. patients <18 years old

2. pregnant women

3. male patients

4. women with T4 disease, including inflammatory breast cancer

5. women who have declined or otherwise not received preceding surgery

6. women with positive margins after primary surgery

7. women with node negative disease

8. women without histologic confirmation of nodal involvement

9. women more than 180 days out from primary breast surgery or adjuvant chemotherapy

10. patients with clinically detected or suspicious lymph node involvement not readily
amenable to surgical treatment (≥cN2 disease)

11. patients with synchronous bilateral breast cancers

12. patients with prior ipsilateral thoracic or breast radiation

13. patients with distant metastatic disease (cM1) or a life expectancy of less than 5
years

14. active collagen vascular disease, specifically dermatomyositis with a creatine
phosphokinase (CPK) level above normal or with an active skin rash, systemic lupus
erythematosis, or scleroderma.

15. other non-malignant systemic disease that would preclude the patient from receiving
study treatment or would prevent required follow-up.

16. patients with psychiatric or addictive disorders or other conditions that, in the
opinion of the Investigator, would preclude the patient from meeting the study
requirements.

17. patients with a separate non-cutaneous cancer diagnosis for which the patient has not
been without evidence of disease for at least 5 years

Note: women <50 years of age, women who received chemotherapy, pN0 (i+ or mol+), and
large-breasted women are eligible for enrollment.