Neurotoxic Effects of Anthracycline- vs Nonanthracycline-Based Chemotherapy on Cognition in Breast Cancer Survivors

Abstract

IMPORTANCE Chemotherapy exposure is a known risk factor for cancer-related cognitive impairments. Anthracycline-based regimens are commonly used chemotherapies that have been shown to be associated with cognitive impairment and brain changes in clinical studies. OBJECTIVE To directly compare the effects of anthracycline and nonanthracycline regimens on cognitive status and functional brain connectivity. DESIGN, SETTING, AND PARTICIPANTS In this observational study, we retrospectively examined cognitive and resting state functional magnetic resonance imaging data acquired from 62 primary breast cancer survivors (mean [SD] age, 54.7 [8.5] years) who were more than 2 years off-therapy, on average. Twenty of these women received anthracycline-based chemotherapy as part of their primary treatment, 19 received nonanthracycline regimens, and 23 did not receive any chemotherapy. Participants were enrolled at a single academic institution (Stanford University) from 2008 to 2014, and the study analyses were performed at this time. MAIN OUTCOMES AND MEASURES Cognitive status was measured using standardized neuropsychological tests, and functional brain connectivity was evaluated using resting state functional magnetic resonance imaging with a focus on the brain’s default mode network. RESULTS The anthracycline group demonstrated significantly lower verbal memory performance including immediate recall (F = 3.73; P = .03) and delayed recall (F = 11.11; P < .001) as well as lower left precuneus connectivity (F = 7.48; P = .001) compared with the other 2 groups. Patient-reported outcomes related to cognitive dysfunction (F = 7.27; P = .002) and psychological distress (F = 5.64; P = .006) were similarly elevated in both chemotherapy groups compared with the non–chemotherapy-treated controls. CONCLUSIONS AND RELEVANCE These results suggest that anthracyclines may have greater negative effects than nonanthracycline regimens on particular cognitive domains and brain network connections. Both anthracycline and nonanthracycline regimens may have nonspecific effects on other cognitive domains as well as certain patient reported outcomes. Further research is needed to identify potential methods for protecting the brain against the effects of various chemotherapeutic agents.

Cognitive Complaints in Survivors of Breast Cancer After Chemotherapy Compared With Age-Matched Controls: An Analysis From a Nationwide, Multicenter, Prospective Longitudinal Study

“…It is possible that these factors are most important in determining the overall impact of cognitive impairment on QOL as well as how others, for example, caregivers, view the patient's cognitive function. Whereas research demonstrates that anthracycline agents are more inflammatory 27,28 and neurotoxic 18 than nonanthracyclines, our study shows patients being treated with either regimen experience CRCI similarly. In addition, those who received hormone therapies and/or radiation therapy after chemotherapy did not experience CRCI statistically differently from those who did not receive these modalities.…”

“…We also hypothesized that patients who received anthracyclines-thought to be cardiotoxic and neurotoxic [15][16][17][18] -would lead to more cognitive complaints than in those who received nonanthracycline regimens.…”

Impact of Physical Inactivity on the Multifactorial Process of Developing Cancer-Related Cognitive Impairments

“…Current data suggests that especially anthracycline-based chemotherapeuticregimes have a negative effect on verbal memory performance and left precuneus connectivity [58]. Furthermore, the exact influence of hormone therapies is still unknown and therefore their exact role remains to be determined [3].…”

Depression Involved in the Chemotherapy Induced Event-based Prospective Memory Impairment in Breast Cancer Survivors

“…Lekovich et al 21 statistically analyzed the incidence of depression in 95 BC patients within 1-6 months after chemotherapy, and reported it to be up to 67%. Recently, certain studies have found that depression in BC patients was not temporary, and some patients have even exhibited high levels of depressive symptoms after the completion of treatment [22][23][24] .…”