NEW YORK (GenomeWeb) – A team from the US, UK, and Switzerland has identified a variant that appears to be associated with congestive heart failure in anthracycline-treated breast cancer patients, pointing to a potential biomarker candidate for the chemotherapy-induced heart problem.
The researchers did a genome-wide association study involving thousands of anthracycline chemotherapy-treated women with breast cancer, searching for variants linked to congestive heart failure. In a discovery group and two validation cohorts, they found that the chromosome 15 variant rs28714259 was somewhat over-represented in patients with congestive heart failure or related heart problems — results they reported today in the journal Clinical Cancer Research.
"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," first author Bryan Schneider, a researcher at Indiana University School of Medicine, said in a statement.
Schneider noted that the team is now following up on findings from the current study in individuals treated with anthracycline chemotherapy at Indiana University's Melvin and Bren Simon Cancer Center to gauge information conveyed by the potential marker relative to other risk factors and co-morbidities already implicated in heart failure risk.
"[A]dditional 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, explaining that metrics used to determine heart damage in relation to long-term outcomes differed somewhat in the clinical trials included in the analysis, while a relatively small number of congenital heart failure cases were included.
For their analyses, Schneider and his colleagues brought together array-based genotyping data for 3,431 women with breast cancer, enrolled in a phase III Eastern Cooperative Oncology Group clinical trial, who were treated with an anthracycline chemotherapy called doxorubicin.
They noted that 68 of these patients — just shy of 2 percent — developed congestive heart failure, on par with past studies of doxorubicin-induced congenital heart failure that have documented the condition in some 1.7 to 2.1 percent of individuals treated with the anthracycline drug.
When the team compared variant patterns in the 51 doxorubicin-treated individuals of European descent who developed congestive heart failure with the remaining European-American patients who did not, it narrowed in on two candidate markers for heart failure risk that were subsequently tested in a validation cohort that included 2,415 genotyped patients and 47 individuals with congestive heart failure following doxorubicin treatment.
The researchers saw a borderline association between congestive heart failure and a SNP known as rs28714259 in the anthracycline-treated breast cancer patients from the discovery and validation cohorts. The variant was more significantly associated with a heart damage-related condition called low ventricular ejection fraction in a third cohort comprised of 828 more breast cancer patients treated with doxorubicin.
"Future confirmatory studies might focus on even less severe phenotypes of cardiac damage," the authors wrote, "as prior data demonstrate that asymptomatic [congenital heart failure] has a marked increase [in] 10-year mortality."