Breast Cancer Clinical Trial
Official title:
B-Receptor Signaling in Cardiomyopathy
We hope to determine the importance of different genes (including B receptors) in anthracycline-induced cardiomyopathy. This has important benefits to patients exposed to anthracyclines, as this could help determine whether certain individuals have increased susceptibility to cardiac injury.
There is a strong correlation between total doxorubicin dose and anti-tumor efficacy,
however, the clinical utility of doxorubicin is severely limited by its cardiotoxicity. With
improved methods of detecting subtle changes in cardiac function, e.g. alterations in left
ventricular wall stress (1), the incidence of doxorubicin cardiotoxicity is now appreciated
to be much higher than previously suspected, documented in 65% of long-term survivors of
childhood cancer, even at doses as low as 228 mg/m2. This cardiotoxicity is dose-related,
and higher doses are related to a higher incidence of clinical heart failure (2).
Doxorubicin's cardiotoxicity is thought to be mediated through the generation of free
radicals and through mitochondrial and membrane damage.
We wish to determine whether beta-receptor genotype affects anthracycline-induced
cardiomyopathy. We will correlate beta-receptor genotype with difference in wall stress
post-anthracycline exposure, and with difference in shortening fraction. We plan to recruit
300 patients over a two-year period. Inclusion criteria includes past exposure to
anthracycline for cancer treatment and an echocardiogram 6 - 48 months after exposure to
anthracyclines.
The mean difference in 1.) wall stress and 2.) shortening fraction between each minor allele
subgroup and wild type subgroup, for both beta-1 and beta-2 will be assessed using unpaired
t-test analyses . We will assess through multivariate linear regression whether there are
interactions between differences in wall stress or fractional shortening and other variables
such as age, gender, dose of anthracycline, type of anthracycline given, and time between
anthracycline exposure and echocardiogram. Those who receive other cardiotoxic drugs (such
as trastuzumab for breast cancer) will be analyzed separately.
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