Effects of NRG-1beta on Chemotherapy-Induced Cardiotoxicity in Patients with Breast Cancer Receiving Trastuzumab and/or Anthracycline-Containing Regimens

PRIMARY OBJECTIVES:

I. To determine the longitudinal relationships between circulating NRG-1beta levels and incident risk of adverse cardiovascular outcomes in patients exposed to anthracycline, trastuzumab, or a combination of the two agents.

II. To study the single nucleotide polymorphism (SNP)/haplotype variation in the neuregulin/epidermal growth factor receptor (ErbB) signaling pathway on incident risk of adverse cardiovascular outcomes.

III. To determine the longitudinal relationships between echocardiographic measures of strain and strain rate and incident cardiac dysfunction in patients exposed to anthracycline, trastuzumab, or a combination of the two agents.

IV. To explore the changes in NRG-1beta levels and the relationships with novel echocardiographic measures of cardiac function.

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

VI. To determine the long-term effects of cancer therapy cardiotoxicity by following patients yearly for a total of

5 years after their exposure to cancer therapy.

OUTLINE:

Patients with additional trastuzumab exposure undergo echocardiogram before treatment, and then at approximately 3, 6, 9, 12, and/or 15 months after treatment. Patients without any additional exposure to trastuzumab undergo echocardiogram before treatment, and then at approximately 4-6 and 12 months after treatment. All patients also undergo collection of blood and plasma samples for analysis of NRG-1beta via enzyme-linked immunosorbent assay (ELISA) every 4-6 weeks during treatment and then once yearly after the initial 15 months of the study, for up to 4 years.

After completion of study, patients are followed up yearly for 4 years.