A Study to Determine the Clinical Significance of Molecular Detection of Breast Cancer in the Blood of Stage IV Breast Cancer Patients

Enrollment Stage IV breast cancer patients who have measurable breast cancer metastases and
are initiating a regimen of systemic therapy are eligible for enrollment.

Phlebotomy Peripheral blood will be obtained from all subjects at the time of initial
enrollment, and at serial time-points during follow-up. The first specimen will be drawn
prior to the initiation of systemic therapy, and subsequent specimens will be obtained
approximately every 6 weeks for approximately 12 weeks depending on the type and schedule of
systemic therapy. Results of molecular analyses will not be available to clinical
investigators.

Systemic Therapy Subjects initiating hormone therapy, chemotherapy, and/or immunotherapy are
eligible for participation.

Restaging Results of patient imaging obtained as part of standard clinical care will be
collected as available.

Survival Analysis Subjects will be followed for at least one year following enrollment. All
clinical and radiographic data will be reviewed in order to determine the clinical response
to therapy. Kaplan-Meier survival estimates will be compared with log-rank testing.

Inclusion Criteria:

Inclusion Criteria - Stage IV breast cancer patients

1. Patient age must be > 21 years.

2. Patient must have a tissue diagnosis of invasive breast cancer.

3. Patient must have documented evidence of metastatic disease.

4. Patient must have measurable lesions.

5. Patients must be initiating systemic therapy. Patients receiving hormonal therapy,
and/or first-,second-, or third-line chemotherapy alone or in combination with other
therapies are eligible.

6. Patient must have an ECOG performance status of 0, 1, or 2.

7. Patient must be available for follow-up.

8. Patient or their authorized legally acceptable representative must consent to be in
the study and must have signed and dated an approved consent form which conforms to
federal and institutional guidelines.

9. The patient with a previous history of non-breast malignancy is eligible for this
study only if the patient meets the following criteria for a cancer survivor. A
cancer survivor is eligible provided the following criteria are met: (1) patient has
undergone potentially curative therapy for all prior malignancies, (2) patients have
been considered disease free for at least 5 years (with the exception of basal cell
or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix).

Inclusion Criteria - Healthy volunteers

A volunteer will be eligible for inclusion in this study only if ALL of the following
criteria apply:

1. Volunteer age must be > 21 years.

2. Volunteer or their authorized legally acceptable representative must consent to be in
the study and must have signed and dated an approved consent form which conforms to
federal and institutional guidelines.

3. Patients with benign breast disease are eligible for enrollment. Patients with benign
breast disease are defined as those patients who are scheduled to undergo a breast
tissue sampling procedure. Breast tissue sampling procedures may include fine needle
aspiration biopsy, core needle biopsy, including image-guided core needle biopsy, and
open surgical biopsy including needle-localization biopsy, and/or excisional biopsy.

4. The volunteer with a previous history of non-breast malignancy is eligible for this
study only if the patient meets the following criteria for a cancer survivor. A
cancer survivor is eligible provided both of the following criteria are met: (1)
patient has undergone potentially curative therapy for all prior malignancies, (2)
patient has been considered disease free for at least 5 years (with the exception of
basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the
cervix).

Exclusion Criteria:

Exclusion Criteria - Stage IV breast cancer patients

A patient will be ineligible for inclusion in this study if ANY of the following criteria
apply:

1. No documented metastatic disease.

2. No measurable lesions.

3. Bone only and/or brain metastasis.

4. Patient is not initiating a new regimen of systemic therapy.

5. Patient has failed 3 regimens of chemotherapy for metastatic disease, not including
adjuvant therapy.