Default mode network connectivity distinguishes chemotherapy-treated breast cancer survivors from controls

Kesler, Shelli R.; Wefel, Jeffrey S.; Hosseini, S. M. Hadi; Cheung, Michael K.; Watson, Christa; Hoeft, Fumiko

doi:10.1073/pnas.1214551110

Cited by 105 publications

(106 citation statements)

References 44 publications

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“…Functional connectivity preprocessing was performed using Statistical Parametric Mapping 8 (SPM8, RRID:SCR_007037) and CONN Toolbox (RRID:SCR_009550) as previously described (Kesler & Blayney, 2015; Kesler et al., 2013, 2014). Successful normalization was confirmed via visual inspection using the check registration function in SPM8 and in‐house software that creates whole volume slice montages.…”

Section: Methodsmentioning

confidence: 99%

Disrupted brain network functional dynamics and hyper‐correlation of structural and functional connectome topology in patients with breast cancer prior to treatment

et al. 2017

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IntroductionSeveral previous studies have demonstrated that cancer chemotherapy is associated with brain injury and cognitive dysfunction. However, evidence suggests that cancer pathogenesis alone may play a role, even in non‐CNS cancers.MethodsUsing a multimodal neuroimaging approach, we measured structural and functional connectome topology as well as functional network dynamics in newly diagnosed patients with breast cancer. Our study involved a novel, pretreatment assessment that occurred prior to the initiation of any cancer therapies, including surgery with anesthesia. We enrolled 74 patients with breast cancer age 29–65 and 50 frequency‐matched healthy female controls who underwent anatomic and resting‐state functional MRI as well as cognitive testing.ResultsCompared to controls, patients with breast cancer demonstrated significantly lower functional network dynamics (p = .046) and cognitive functioning (p < .02, corrected). The breast cancer group also showed subtle alterations in structural local clustering and functional local clustering (p < .05, uncorrected) as well as significantly increased correlation between structural global clustering and functional global clustering compared to controls (p = .03). This hyper‐correlation between structural and functional topologies was significantly associated with cognitive dysfunction (p = .005).ConclusionsOur findings could not be accounted for by psychological distress and suggest that non‐CNS cancer may directly and/or indirectly affect the brain via mechanisms such as tumor‐induced neurogenesis, inflammation, and/or vascular changes, for example. Our results also have broader implications concerning the importance of the balance between structural and functional connectome properties as a potential biomarker of general neurologic deficit.

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Section: Methodsmentioning

confidence: 99%

Disrupted brain network functional dynamics and hyper‐correlation of structural and functional connectome topology in patients with breast cancer prior to treatment

et al. 2017

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“…Research in this domain has traditionally focused on the chronic psychosocial late effects, such as impairments in quality of life, persistent fatigue, depression, and anxiety (Day et al 1999; Ganz et al 1995, 1998; Goodwin et al 2003; Land et al 2006). More recent research endeavors have broadened to include investigation of long-term cognitive impairments in early breast cancer patients (Ahles et al 2002; Jim et al 2012; Phillips et al 2012; Kesler et al 2013). This work has demonstrated that standard breast cancer adjuvant therapy, particularly treatment with chemotherapy, is associated with adverse cognitive functioning, including impairments in memory, processing speed, and executive function (Ahles et al 2002; Jim et al 2012; Phillips et al 2012), which may persist up to 20 years following the completion of primary adjuvant therapy (Koppelmans et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Relationship between exercise behavior, cardiorespiratory fitness, and cognitive function in early breast cancer patients treated with doxorubicin-containing chemotherapy: a pilot study

Crowgey

Peters

Hornsby

et al. 2014

Appl. Physiol. Nutr. Metab.

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The purpose of this study was to examine the relationship between self-reported exercise behavior, cardiorespiratory fitness (CRF), and cognitive function in early breast cancer patients. Thirty-seven breast cancer patients following completion of chemotherapy (median 16 months) and 14 controls were studied. Cognitive function was assessed using the Central Nervous System (CNS) Vital Signs software (CNS Vital Signs, LLC, Morrisville, N.C., USA), a computerized test battery consisting of 9 cognitive subtests. Exercise behavior was evaluated using the Godin Leisure Time Exercise Questionnaire, and CRF was assessed via a cardiopulmonary exercise test to assess peak oxygen consumption. Patients’ mean total exercise was 184 ± 141 min·week−1 compared with 442 ± 315 min·week−1 in controls (p < 0.001). Significantly fewer patients (32%) were meeting exercise guidelines (i.e., ≥150 min of moderate-intensity or vigorous exercise per week) compared with 57% of controls (p = 0.014). Patients’ peak oxygen consumption averaged 23.5 ± 6.3 mL·kg−1·min−1 compared with 30.6 ± 7.0 mL·kg−1·min−1 in controls (p < 0.01). Scores on the cognitive subdomains were generally lower in patients compared with controls, although only the difference in verbal memory was significant (unadjusted p = 0.041). In patients, weak to moderate correlations were indicated between exercise, peak oxygen consumption, and the majority of cognitive subdomain scores; however, there was a significant positive correlation between exercise and visual memory (r = 0.47, p = 0.004). In conclusion, breast cancer patients following the completion of primary adjuvant chemotherapy exhibit, in general, worse cognitive performance than healthy women from the general population, and such performance may be related to their level of exercise behavior.

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“…1–5 These cognitive impairments can be long-lasting and tend to be one of the most common limitations to quality of life and well-being. 6,7 There is growing concern that chemotherapy may increase the risk for later neurodegenerative conditions by altering or accelerating brain-aging processes.…”

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confidence: 99%

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

2016

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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.

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Default mode network connectivity distinguishes chemotherapy-treated breast cancer survivors from controls

Cited by 105 publications

References 44 publications

Disrupted brain network functional dynamics and hyper‐correlation of structural and functional connectome topology in patients with breast cancer prior to treatment

Disrupted brain network functional dynamics and hyper‐correlation of structural and functional connectome topology in patients with breast cancer prior to treatment

Relationship between exercise behavior, cardiorespiratory fitness, and cognitive function in early breast cancer patients treated with doxorubicin-containing chemotherapy: a pilot study

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

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