Cardiotoxicity of Cancer Therapy (CCT)

The overall study objectives are:

1. To determine the longitudinal relationships between circulating markers, such as
NRG-1Beta levels and incident risk of adverse cardiovascular outcomes in patients
exposed to anthracycline, trastuzumab, or a combination of the two agents. We
hypothesize that a sustained increase in NRG-1Beta, indicative of enhanced cardiac
stress with exposure to chemotherapeutic agents, is predictive of an increased risk of
cardiac dysfunction and heart failure.

2. To study the SNP/haplotype variation in pathways of interest, such as the
Neuregulin/ErbB signaling pathway, on incident risk of adverse cardiovascular outcomes.
We hypothesize that there will be SNP/haplotypes variations that are associated with
incident cardiovascular outcomes.

3. To determine the longitudinal relationships between novel echocardiographic measures,
such as strain and strain rate and incident cardiac dysfunction in patients exposed to
anthracycline, trastuzumab, or a combination of the two agents. We hypothesize that
early declines in strain and strain rate are predictive of an increased risk of future
cardiac dysfunction and heart failure.

4. To explore the changes in biomarkers such as NRG-1Beta levels and the relationships with
novel echocardiographic measures of cardiac function.

5. To create a biobank as a future resource for additional questions in novel biomarkers
and genetics.

6. To determine the long-term effects of cancer therapy cardiotoxicity by following
patients yearly for 5 years after their exposure to cancer therapy, with the option to
extend up to an additional 5 years.

Inclusion Criteria:

- Age 18 years or older

- HER-2 positive breast cancer designated to receive trastuzumab chemotherapy with or
without prior exposure to anthracycline-based chemotherapy

- Non-HER-2 positive breast cancer designated to receive treatment with an
anthracycline-containing regimen

Exclusion Criteria:

- Pre-existing cardiomyopathy with a left ventricular ejection fraction of less than
50%.

- Other contraindications to trastuzumab or anthracycline chemotherapy.