Anthracycline-based Chemotherapy More Likely to Produce Neurotoxic Effects on Cognition in Breast Cancer Survivors

Anthracycline-based chemotherapy may have greater negative effects on some cognitive domains and brain network connections compared with nonanthracycline-based regimens, according to an article published by JAMA Oncology (doi:10.1001/jamaoncol.2015.4333).

Cognitive impairment related to cancer is often called chemobrain, and chemotherapy for breast cancer is often associated with cognitive problems. However, whether certain regimens are associated with greater cognitive difficulties than others is unclear.

Shelli R. Kesler, PhD, of the University of Texas MD Anderson Cancer Center in Houston, and Douglas W. Blayney, MD, of the Stanford University School of Medicine in California, compared the effects of anthracycline and nonanthracycline chemotherapy regimens on cognitive status and functional brain connectivity.

The authors used cognitive tests and imaging data from 62 primary breast cancer survivors (average age 55 years) whose therapy was completed, on average, more than 2 years ago to examine cognitive status and functional brain connectivity. In the study, 20 women received anthracycline-based chemotherapy as part of their primary treatment, 19 women received nonanthracycline regimens, and 23 women did not receive any chemotherapy.

Women treated with anthracycline-based chemotherapy had lower verbal memory, including both immediate and delayed recall, compared with the other 2 groups of women. The anthracycline regimens also were associated with lower default-mode brain network connectivity, which suggested a decreased efficiency of information processing.

Patient-reported outcomes of cognitive dysfunction and psychological distress were elevated in both groups of women treated with chemotherapy compared with patients treated without chemotherapy, the results indicate.

“These results should be considered preliminary given the study limitations of small sample size and retrospective, cross-sectional design. Larger, prospective studies are needed that include pretreatment and posttreatment assessments so that patients' individual cognitive and neurobiologic trajectories can be evaluated with respect to potential ANTHR [anthracycline]-related neurotoxic effects,” the study concluded. The study was supported by grants from the National Institutes of Health.

In a related editorial (doi:10.1001/jamaoncol.2015.4551), Andrew J. Saykin, PsyD, of the Indiana University School of Medicine in Indianapolis, and coauthors wrote, “While previous studies have linked chemotherapy and cognitive decline, and a few other studies have linked treatment with differences in brain connectivity, there has been very little research comparing cognitive effects of different types and combinations of chemotherapy because most studies have been underpowered to distinguish these effects. This present study builds on preclinical work and, although modest in power to detect regimen differences, represents an important step forward while underscoring the need for larger studies.”

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