December 20, 2016

Genetic Biomarker Identifies Patients at Risk for Anthracycline-Induced Congestive Heart Failure

PHILADELPHIA -- December 20, 2016 -- Among women with breast cancer who received anthracycline chemotherapy, those who had a certain genetic biomarker had a significantly increased risk for having anthracycline-induced congestive heart failure, according to a study published in the journal Clinical Cancer Research.

Bryan P. Schneider, MD, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, 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. As a result, the more information a patient and his or her oncologist have about the potential risks and benefits of treatment the better prepared they are to make good treatment decisions, he noted.

“Anthracyclines such as doxorubicin, which are widely used chemotherapeutic agents, cause congestive heart failure in about 1% to 2% of patients,” said Dr. Schneider. “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.”

The researchers analysed genome-wide association data from 3,431 women with breast cancer who received doxorubicin as part of treatment received through enrolment in the phase 3 Eastern Cooperative Oncology Group (ECOG) 5103 clinical trial and for whom heart assessment data were available. Among these patients, 68 (2%) had cardiologist-adjudicated congestive heart failure.

Because the majority of those who had cardiologist-adjudicated congestive heart failure (n = 51) were European-American, the researchers limited the genetic association analysis to European-Americans.

The researchers identified several SNPs associated with risk of anthracycline-induced congestive heart failure. After looking at the chromosomal location of the SNPs, the researchers chose 2 of the top SNPs for validation in independent data sets.

One of the 2 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 enrolment in the phase 3 ECOG 1199 clinical trial. It was also associated with low ventricular ejection fraction among 828 women with breast cancer who received doxorubicin as part of treatment through enrolment in the phase 3 BEATRICE clinical trial.

“We found that the A allele of the SNP rs28714259 was associated with increased risk of anthracycline-induced congestive heart failure among women with breast cancer,” said Dr. Schneider. “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. 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 noted 2 main study 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, 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,” he said.

SOURCE: American Association for Cancer Research

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