Cancer-related cognitive impairment, often called “chemobrain,” may be more pronounced after anthracycline-based chemotherapy than after nonanthracycline regimens, affecting specific memory functions and brain network connectivity, a study reported in JAMA Oncology suggests.
Cognitive complaints are commonly reported by breast cancer survivors who received chemotherapy, but it has been unclear whether some chemotherapy regimens produce greater lasting cognitive effects than others. Researchers compared cognitive test results and resting-state brain connectivity among breast cancer survivors treated with anthracycline-based chemotherapy, survivors treated with other chemotherapy regimens, and survivors who did not receive chemotherapy.
Shelli R. Kesler, Ph.D., of the University of Texas MD Anderson Cancer Center, and Douglas W. Blayney, M.D., of Stanford University School of Medicine, examined standardized neuropsychological test scores and functional magnetic resonance imaging (fMRI) measures from 62 women who had completed primary treatment for breast cancer. The women were, on average, 54.7 years old and were assessed more than two years after finishing therapy. Of these participants, 20 had received anthracycline-containing chemotherapy, 19 had received nonanthracycline regimens, and 23 had not received chemotherapy.
On objective testing, women who had received anthracycline-based chemotherapy scored lower on verbal memory measures, including both immediate and delayed recall, compared with the two other groups. Functional brain imaging showed reduced connectivity within the brain’s default mode network—particularly lower connectivity in the left precuneus—in the anthracycline group. Reduced default mode network connectivity is commonly interpreted as diminished efficiency in the brain networks that support memory and internally directed cognition.
Self-reported measures mirrored some of the objective findings: participants who had undergone any chemotherapy (both anthracycline and nonanthracycline groups) reported greater cognitive problems and higher psychological distress compared with those who had not received chemotherapy. This pattern suggests that while anthracycline regimens may produce stronger effects on particular cognitive domains and network connections, chemotherapy in general can be associated with broader subjective cognitive complaints and emotional distress.
The authors emphasize that these findings are preliminary. The study’s retrospective, cross-sectional design and relatively small sample size limit the ability to draw definitive causal conclusions. The researchers note the need for larger, prospective investigations that assess patients before and after treatment so that individual cognitive and neurobiological trajectories can be tracked and potential neurotoxic effects of specific agents, such as anthracyclines, can be more clearly established.
Source: Laura Sussman – JAMA Network
Image Source: The image is credited to Nicki Dugan Pogue and is licensed CC BY SA 2.0
Original Research: Abstract for “Neurotoxic Effects of Anthracycline- vs Nonanthracycline-Based Chemotherapy on Cognition in Breast Cancer Survivors” by Shelli R. Kesler, PhD and Douglas W. Blayney, MD in JAMA Oncology. Published online December 3, 2015. doi:10.1001/jamaoncol.2015.4333
Abstract
Neurotoxic Effects of Anthracycline- vs Nonanthracycline-Based Chemotherapy on Cognition in Breast Cancer Survivors
Importance Exposure to chemotherapy is a recognized risk factor for cancer-related cognitive impairment, commonly termed chemobrain. Anthracycline-based regimens are widely used in breast cancer treatment and have been implicated in cognitive changes and brain imaging abnormalities in prior clinical research.
Objective To compare directly the cognitive and resting-state functional brain connectivity outcomes associated with anthracycline-based versus nonanthracycline chemotherapy regimens in breast cancer survivors.
Design, Setting, and Participants This observational, retrospective study analyzed cognitive testing and resting-state fMRI data from 62 primary breast cancer survivors (mean age 54.7 years) who were, on average, more than two years post-therapy. Participants were enrolled at Stanford University between 2008 and 2014. The sample included 20 women treated with anthracycline-based chemotherapy, 19 treated with nonanthracycline regimens, and 23 who did not receive chemotherapy.
Main Outcomes and Measures Standardized neuropsychological tests assessed cognitive domains such as verbal memory, while resting-state fMRI evaluated functional connectivity with a focus on the default mode network, a set of brain regions implicated in memory and self-referential cognition.
Results Compared with the nonanthracycline and no-chemotherapy groups, the anthracycline group showed significantly lower verbal memory performance (immediate recall: F = 3.73, P = .03; delayed recall: F = 11.11, P < .001) and reduced left precuneus connectivity (F = 7.48, P = .001). Patient-reported cognitive dysfunction (F = 7.27, P = .002) and psychological distress (F = 5.64, P = .006) were elevated in both chemotherapy groups relative to controls who did not receive chemotherapy.
Conclusions and Relevance The findings indicate that anthracycline-based chemotherapy may exert greater negative effects on specific cognitive domains—particularly verbal memory—and on default mode network connectivity than nonanthracycline regimens. Both major categories of chemotherapy were associated with increased subjective cognitive complaints and psychological distress. Further prospective research is needed to confirm these observations, to characterize agent-specific neurotoxic effects, and to develop interventions that protect cognitive function in cancer survivors.