Anthracyclines Negatively Impact Brain Function

Cancer survivors treated with anthracycline-based chemotherapies exhibited poorer performance of certain cognitive skills compared with survivors who received no chemotherapy or other classes of chemotherapies, according to the results of a study published in JAMA Oncology.

While the study of 62 primary breast cancer survivors is retrospective and small, the results suggest that further studies are needed to understand how the neurologic effects of anthracycline-based chemotherapy agents may be minimized.

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 Stanford, California, analyzed both cognitive function and resting state functional magnetic resonance brain imaging data from breast cancer survivors who were treated, on average, 2.1 years prior to undergoing the assessments. The patients were all assessed at Stanford University.

Twenty patients had received anthracycline-based chemotherapy, 19 had received other types of chemotherapies, and 23 had no chemotherapy. Patients received an average of 6 chemotherapy cycles and had an average age of 52, 53, and 58 years in the anthracycline, non-anthracycline, and no-chemotherapy groups, respectively.

Patients who received anthracyclines had a significantly lower verbal memory performance, including immediate recall (P = .03) and delayed recall (P < .001) compared with the other two groups. The anthracycline-treated patients also had lower connectivity in certain brain regions at resting state. Patients in both chemotherapy groups reported greater cognitive dysfunction (P = .002) and psychological stress (P = .006) compared with the 23 patients in the no-chemotherapy group.

Anthracycline-based chemotherapy regimens, such as those containing doxorubicin, are often used to treat breast cancer patients; prior studies have suggested that these regimens may be associated with cognitive impairment, yet cognition impairment outcomes in these patients have not been directly compared with those of patients treated with other types of chemotherapy regimens. The current study results suggest that there may be differences in outcomes with different types of chemotherapies, but the authors emphasize that the current work is preliminary and only larger prospective trials will provide data on how chemotherapies affect the brain and which types of treatments may result in cognitive dysfunction.

In an accompanying editorial, Andrew J. Saykin, PsyD, of the Indiana University School of Medicine in Indianapolis, and coauthors agreed that few studies have compared the cognitive effects of different types of chemotoxic agents used to treat cancer.

“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,” they wrote.