The primary objectives of this study are:

1. To determine whether tissue Doppler imaging and/or circulating levels of B-type natriuretic peptide, or its byproduct aminoterminal pro-B-type natriuretic peptide, and ultrasensitive troponin are early and sensitive markers of cardiac toxicity in breast cancer patients treated with trastuzumab (Herceptin). We hypothesize that early abnormalities of tissue Doppler imaging and/or natriuretic peptides or troponin will predict a later decrease in left ventricular function.
2. To test whether metabolic profiling can predict or detect in an early manner treatment-induced cardiac toxicity in breast cancer patients.
3. To determine whether common HER-2 single nucleotide polymorphisms identify a subgroup of breast cancer patients at high risk developing cardiac toxicity with Herceptin therapy.
4. To determine whether Herceptin infusion causes acute changes in cardiac function.

Echocardiogram:

Because of the heart-related side effects of chemotherapy and trastuzumab, your regular doctor will monitor your heart's function as part of your routine care. You will have echocardiograms performed before you begin treatment, and then every 3 months. An echocardiogram uses sound waves to check your heart's health.

If you decide to take part in this study, researchers will take several additional pictures of your heart during each of your regularly scheduled echocardiograms. The additional pictures will make the procedure take about 5-10 minutes longer than the regular echocardiogram. These pictures will be viewed in a different way than the standard echocardiogram pictures. Researchers hope viewing the pictures this way can help researchers to find heart problems earlier than the usual tests.

Blood Tests:

Blood (about 4 teaspoon each time) will be drawn during the routine blood draw that occurs closest to the regularly scheduled echocardiograms.

The heart produces hormones called BNP and NT-proBNP. These hormones can be measured in the blood. BNP and NT-proBNP levels can be higher when the heart is not working as well. Researchers will measure these hormones at the time of each echocardiogram. Researchers hope to learn whether measuring these hormones can help identify the heart-related side effects of chemotherapy and trastuzumab earlier than the usual tests.

Researchers will also measure metabolic proteins (such as sugars and acids) in the blood. Researchers hope to learn whether measuring these metabolic proteins can help identify the heart-related side effects of chemotherapy and trastuzumab earlier than the usual tests.

Because protein, sugar or acid levels may be temporarily changed after you eat, you will be asked not to eat overnight before having your blood drawn.

Study Visits:

You will have 6 study visits around the time that you have an echocardiogram. These visits will occur before you take Herceptin, when you begin Herceptin, and 3, 6, 9, and 12 months later. These study visits will be scheduled on days when you are already making a visit to your regular doctor.

You will not have to make any special visits to the hospital for this research study.

During each study visit, you will be asked about any symptoms you may be experiencing, and any medications you may be taking. Your blood pressure and heart rate will be measured.

Length of Study:

You will be considered off-study once you complete the 6 study visits.

THIS IS AN INVESTIGATIONAL STUDY. Up to 100 patients will take part in this multicenter study. Up to 20 patients will be enrolled at M. D. Anderson.

• Procedure: Echocardiograms
• Procedure: Blood Test

Inclusion Criteria:

1. Age 18 years or older
2. HER-2 positive breast cancer
3. Scheduled to receive Herceptin infusion therapy after exposure to anthracycline-based chemotherapy in one of the following manners: Adjunctive treatment for early stage disease with anthracycline-based chemotherapy followed by Herceptin infusion therapy. Herceptin monotherapy in patients with metastatic disease previously treated with anthracycline-based chemotherapy. Herceptin in combination with non-anthracycline chemotherapy in patients with metastatic disease previously treated with anthracycline-based chemotherapy
4. Normal baseline left ventricular ejection fraction

Exclusion Criteria:

1. Pre-existing cardiomyopathy (LVEF < 50%)
2. Other contraindication to Herceptin therapy