Identifying Patients at Risk for Life-threatening Adverse Effect of Chemotherapy
A new genetic biomarker identified breast cancer patients at increased risk for heart damage caused by anthracycline chemotherapy.
Women with breast cancer who had a certain genetic biomarker had a significantly increased risk of suffering congestive heart failure as a result of treatment with a class of chemotherapy agents called anthracyclines, according to a study published in Clinical Cancer Research, a journal of the American Association for Cancer Research.
“Anthracyclines such as doxorubicin, which are widely used chemotherapeutic agents, cause congestive heart failure in about 1 to 2 percent of patients,” said lead author of the study, Bryan P. Schneider, MD, associate professor of medicine at the Indiana University Melvin and Bren Simon Cancer Center in Indianapolis. “Knowing which patients are at increased risk for this life-threatening effect of anthracycline chemotherapy is important to help oncologists counsel patients about their personal risks and benefits of such treatment.
“We found that the A allele of the single nucleotide polymorphism (SNP) rs28714259 was associated with increased risk of anthracycline-induced congestive heart failure among women with breast cancer,” he added.
Dr. Schneider explained that the decision to undergo chemotherapy for breast cancer is not always clear cut because each patient has a different risk of relapse and different tolerance to potential adverse effects of treatment.
“Adding information gained from testing for this SNP to currently used clinical information could help oncologists provide a more precise prediction of the risks and benefits of anthracycline chemotherapy for patients with breast cancer,” he said. “We are currently further testing this finding in patients receiving anthracyclines at the Indiana University Melvin and Bren Simon Cancer Center to better understand its contribution to heart failure risk in the face of other known risk factors and comorbidities.”
Dr. Schneider and his colleagues analyzed genome-wide association data from 3,431 women with breast cancer who received doxorubicin as part of treatment received through enrollment in the phase III Eastern Cooperative Oncology Group (ECOG) 5103 clinical trial and for whom heart assessment data were available. Among these patients, 68 (2 percent) had cardiologist-adjudicated congestive heart failure.
Because the majority of those who had cardiologist-adjudicated congestive heart failure (51) were European-American, the researchers limited the genetic association analysis to European- Americans. They identified several SNPs associated with risk of anthracycline-induced congestive heart failure.
After looking at the chromosomal location of the SNPs, the researchers chose two of the top SNPs for validation in independent data sets.
One of the two SNPs, rs28714259 was associated with risk of anthracycline-induced congestive heart failure among 2,415 women with breast cancer who received doxorubicin as part of treatment received through enrollment in the phase III ECOG 1199 clinical trial. It was also associated with low ventricular ejection fraction, which is a sign of heart damage, among 828 women with breast cancer who received doxorubicin as part of treatment through enrollment in the phase III BEATRICE clinical trial.
According to Dr. Schneider, the study has two main limitations. First, not all of the clinical trials used the same method for assessing heart damage with corresponding long-term data. Second, the number of patients who had heart damage was relatively low because it is a rare adverse event.
“As a result [of the limitiations], additional studies in other patient groups and in the real-world setting of the clinic, as we are doing, are needed to confirm the association,” said Dr. Schneider.