Aggressive Local Therapy for Limited Bone-Only Metastasis to Improve Progression-Free Survival in Breast Cancer Patients

Study Treatments:

Current standard of care for breast cancer patients whose disease has spread to the bones is
to treat them with chemotherapy or endocrine therapy. However, using radiation and surgery as
well may help to get rid of the cancer cells in the bone lesions.

All participants will receive separate consent documents to sign that will explain the
routine surgery, radiation therapy, and chemotherapy.

Standard Therapy:

If the imaging scans show that you are not at increased risk for bone fracture, you will
receive 3 to 9 months of systemic therapy that is most appropriate for you as decided by your
doctor. You may also be placed on endocrine therapy as decided by your doctor. If you have
received drugs in the past that could cause heart-related side effects and/or a history of
heart disease, you may have heart function tests, if your cancer doctor decides it is needed.

Study Visits:

After you have received 3-9 months of standard therapy, you will receive an MRI scan, a
PET/CT scan, an X-ray, and a whole-body bone scan to make sure you still have no more than 3
bone metastases. Blood (about 2 tablespoons) and urine tests will also be collected to make
sure you have no more than 3 bone metastases.

Local Therapy:

If you still have no more than 3 bone metastases, local treatments including high-dose
radiation therapy and/or surgery will be given. The most appropriate local therapy will be
chosen by your treating radiation oncologist, surgeon, and medical oncologist.

For bones with fractures or at risk for fracture, a rod or other devices may be placed in the
bone to fix the bone. Radiation therapy involves daily treatments during weekdays that may
last 5 to 7 weeks in a row. Each daily treatment may last 30 - 40 minutes. For special cases,
shorter courses of radiation therapy may be offered to treat the lesions in the spine.
Radiation types, such as photon, electron, or proton will be selected by your doctor.

If you have a risk of bone fracture due to the cancer, you may be treated with surgery and/or
radiation first, before starting standard therapy. Again, the most appropriate local therapy
will be chosen by your treating radiation oncologist, surgeon, and medical oncologist.

After completing the local therapies, you will receive an MRI scan, a PET/CT scan, a X-ray,
and a whole-body bone scan to make sure you still have no more than 3 bone metastases. Blood
(about 2 tablespoons) and urine will also be collected to make sure you have no more than 3
bone metastases. Then, you will receive 3 to 9 months of systemic therapy that is most
appropriate for you as decided by your doctor. You may also be placed on endocrine therapy as
decided by your doctor.

Length of Study:

The standard systemic therapy treatments may last 3 to 9 months. The radiation therapy
process may last 6 to 8 weeks. Surgery, including recovery, may last 4 to 6 weeks. You will
be taken off study early if you are found to have more than 3 lesions, if the disease
worsens, or if you have intolerable side effects.

Long-Term Follow-up:

After the local and standard therapies are finished, you will have a follow-up visit at 3
months and every 3 months for the 1st year after the therapies, and then every 6 months for
the 2nd and 3rd year after the therapies. At each of these visits, the following tests will
be performed:

- You will have periodic tests which may include an MRI scan, a PET/CT scan, an X-ray, and
a whole-body bone scan to check on the status of the disease. Your doctor will decide
which tests you will need. The tests will be done every 3 months for the first year and
then every 6 months for the next 2 years.

- Blood (about 2 tablespoons) and urine will be collected to check on the status of the
disease.

- You will complete QOL questionnaires.

After the completion of the 36 month visit, you are encouraged to follow-up at any time after
the last visit up to 1 year. Your doctor may request that you have an MRI scan, a PET/CT
scan, an X-ray, and/or a whole-body bone scan to check on the status of the disease.

This is an investigational study. The use of local treatments (surgery and radiation therapy)
to treat metastatic lesions of the bone is investigational. The use of chemotherapy and
endocrine therapy is standard of care for breast cancer patients with metastases.

Up to 75 evaluable patients will take part in this study. All will be enrolled at MD
Anderson.

Inclusion Criteria:

1. Breast cancer with metastasis to skeletal sites only

2. 1 to 3 bone metastatic sites (metastatic lesions in the same bone that are within 3 cm
of each other are considered as one site)

3. KPS greater than or equals to 70

4. Absolute neutrophil count of > 1500 per microliter and platelet count > 100,000 per
microliter; AST and alkaline phosphatase < = 2.5 X normal limits, bilirubin < = 1.5 x
normal limits, calculated creatinine clearance > 50 ml/min using Cockcroft-Gault
formula: CrCl male = (140-age) x (wt. in kg)/(Serum Cr x 72); CrCl female = 0.85 x
(CrCl male)

5. Patients may or may not have started bis-phosphonates.

6. Patients who have received prior chemotherapy for their original breast cancer
treatment are still eligible.

7. Previous use of systemic therapy for bone metastasis is allowable as long as the
systemic therapy use fits within the treatment plan as described in Proposed
Treatment/Study Plan. (If the patient received less than 3 - 9 months of systemic
therapy previously, the use of additional systemic therapy may be necessary to fit
within the treatment plan)

8. Treating physician assesses tumor to be sufficiently distant from sensitive structures
to be able to achieve greater than or equal to 66 Gy. (i.e., spinal cord tolerance
respected in vertebral body metastasis.

9. Patients with immanent risk of fracture(s) may receive local therapy prior to systemic
therapy. Otherwise systemic therapy should be given first as outlined in abstract
treatment study plan sections 1 and 2.

Exclusion Criteria:

1. Distant metastasis to organs (local recurrence and regional lymph node recurrence are
not considered as distant metastasis) other than bone

2. Prior radiation to site(s) of distant metastasis of bone

3. History of scleroderma and systemic lupus erythematosus which increases the risk of
toxicity from radiation treatment

4. Second primary malignancy (skin cancer other than melanoma allowed) that is disease
free for less than 3 years

5. Premenopausal and postmenopausal (amenorrheic for less than 12 months) women with
either a positive or no pregnancy test (serum or urine) at baseline within 7 days
study enrollment. Postmenopausal women who are amenorrheic for more than 12 months do
not require pregnancy test.

6. Women with child-bearing potential not using a reliable an appropriate contraceptive
method.

7. Patients with child-bearing potential will agree to use contraception while on study
and for 30 days from the date of the last therapy on protocol.

8. If the patient requires surgery of the bone metastasis, clinically serious
comorbidities that render patient not medically fit for surgery (e.g. congestive heart
failure, symptomatic coronary artery disease, cardiac arrhythmias and chronic lung
disease not well controlled with medication; myocardial infarction within 12 months of
enrollment)

9. Central nervous system disorders or psychiatric disability judged by the investigator
to be clinically significant to preclude informed consent or interfere with complying
with protocol treatments.