Blood and neuroimaging biomarkers of cognitive sequelae in breast cancer patients throughout chemotherapy: A systematic review

Schroyen, Gwen; Vissers, Julie; Smeets, Ann; Gillebert, Céline R.; Lemiere, Jurgen; Sunaert, Stefan; Deprez, Sabine; Sleurs, Charlotte

doi:10.1016/j.tranon.2021.101297

Cited by 11 publications

(9 citation statements)

References 73 publications

(153 reference statements)

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“…Treatment for breast cancer has been associated with long-term neurocognitive difficulties that are often referred to as “chemo-brain” ( Janelsins et al, 2017 ; Ketterl et al, 2019 ; Eide and Feng, 2020 ; Schroyen et al, 2021 ). Neurocognitive difficulties may encompass memory loss, difficulty concentrating, and other relatively subtle changes that can have a detrimental impact on daily functioning ( Chan et al, 2016 ; Sousa et al, 2020 ) and are negatively associated with HRQOL ( Kunin-Batson et al, 2014 ; Eide and Feng, 2020 ; van der Plas et al, 2020 ; Wagner et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…In their systematic review, Sousa et al (2020) reported that there was no evidence for functional change acutely after chemotherapy for breast cancer, even though brain changes were already noted. Others showed that alterations in blood markers of inflammation and neuronal integrity increased the patients with longer breast cancer that are from diagnosis ( Schroyen et al, 2021 ). The notion of “allostatic load” may explain the lag between physiological changes and functional deficits.…”

Section: Discussionmentioning

confidence: 99%

“…The notion of “allostatic load” may explain the lag between physiological changes and functional deficits. Allostatic load conveys the cumulative impact of physiological “wear and tear” on the brain and body that eventually results in deterioration in physical and mental health ( Suvarna et al, 2020 ; Schroyen et al, 2021 ). Thus, a longitudinal assessment of a wide variety of markers indicative of physiological “wear and tear” (e.g., quantitative neuroimaging, blood markers of brain injury, and subtle cognitive decline) is a promising tool to help preserve HRQOL in young breast cancer survivors.…”

Section: Discussionmentioning

confidence: 99%

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Characterizing Early Changes in Quality of Life in Young Women With Breast Cancer

et al. 2022

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IntroductionYounger age at diagnosis is a risk factor for poor health-related quality of life (HRQOL) in long-term breast cancer survivors. However, few studies have specifically addressed HRQOL in young adults with breast cancer (i.e., diagnosed prior to age 40), nor have early changes in HRQOL been fully characterized.MethodsEligible female patients with breast cancer were identified through our local cancer center. To establish HRQOL, patients completed the Functional Assessment of Cancer Therapy-Breast (FACT-B) around diagnosis and 12 months later. Sociodemographic factors, genetic susceptibility to cancer, tumor- and treatment-related factors, and comorbidities (e.g., depression/anxiety) were abstracted from medical records and the local oncology registry. Mixed-effects models were used to identify changes in FACT-B scores during the first year of treatment and to determine whether any demographic/treatment-related factors modulated changes in scores.ResultsHealth-related quality of life in young patients with breast cancer was within normal limits at baseline, with a FACT-B overall well-being score of 108.5 (95% confidence limits [CI] = 103.7, 113.3). Participants reported slight improvements over a 12-month period: FACT-B overall well-being scores increased 6.6 points (95% CI = 2.1, 11.1, p < 0.01), functional well-being improved 3.0 points (95% CI = 2.0, 4.1, p < 0.01), emotional well-being improved 1.9 points (95% CI = 0.9, 2.8, p < 0.01), and physical well-being improved 1.5 points (95% CI = 0.2, 2.8, p = 0.03), on average. Participants with anxiety/depression at baseline reported greater improvements in FACT-B overall well-being (change: 12.9, 95% CI = 6.4, 9.5) and functional well-being (change: 5.2, 95% CI = 3.5, 6.9) than participants who did not have anxiety/depression at baseline (change in FACT-B overall well-being: 4.9, 95% CI = 0.2, 9.7; change in functional well-being: 2.3, 95% CI = 1.1, 3.4). Marital status, reconstructive surgery, and baseline clinical staging were also significantly associated with changes in aspects of HRQOL, although their impact on change was relatively minimal.ConclusionYoung women with breast cancer do not report HRQOL concerns during the first year of treatment. Improvements in HRQOL during the first year of treatment may be attributable to a sense of relief that the cancer is being treated, which, in the short run, may outweigh the negative late effects of treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Characterizing Early Changes in Quality of Life in Young Women With Breast Cancer

et al. 2022

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“…Indeed, the patterns of increased metabolism observed here are reminiscent of the hypermetabolism observed in the basal ganglia in invasive fungal-infections ( 31 ), suggesting an inflammatory reaction spreading to the putamen. As chemotherapeutic agents are known to induce peripheral inflammation with increasing cytokine levels ( 32 , 33 ), cytokine upregulation may, in part, be responsible for changes in brain glucose metabolism. Indeed, after interferon-α therapy, increased basal ganglia glucose metabolism was observed, while frontal metabolism was reduced ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Cerebral glucose changes after chemotherapy and their relation to long-term cognitive complaints and fatigue

et al. 2022

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PurposeTo investigate the short-term cerebral metabolic effects of intravenous chemotherapy and their association with long-term fatigue/cognitive complaints.Experimental designUsing [18F]-FDG-PET/CT whole-body scans, we retrospectively quantified relative cerebral glucose metabolism before and after neoadjuvant chemotherapy in a cohort of patients treated for non-metastatic breast cancer (2009-2019). Self-report of cognitive complaints and fatigue were prospectively assessed 7 ± 3 years after therapy. Metabolic changes were estimated with i) robust mixed-effects modelling in regions-of-interest (frontal, parietal, temporal, occipital, and insular cortex) and ii) general-linear modelling of whole-brain voxel-wise outcomes. iii) The association between metabolic changes and self-reported outcomes was evaluated using linear regression-analysis.ResultsOf the 667 screened patients, 263 underwent PET/CT before and after chemotherapy and 183 (48 ± 9 years) met the inclusion criteria. After chemotherapy, decreased frontal and increased parietal and insular metabolism were observed (|ß|>0.273, pFDR<0.008). Separately, additional increased occipital metabolism after epiribucin+ cyclophosphamide (EC) and temporal metabolism after EC+ fluorouracil chemotherapy were observed (ß>0.244, pFDR≤0.048). Voxel-based analysis (pcluster-FWE<0.001) showed decreased metabolism in the paracingulate gyrus (-3.2 ± 3.9%) and putamen (3.1 ± 4.1%) and increased metabolism in the lateral cortex (L=2.9 ± 3.1%) and pericentral gyri (3.0 ± 4.4%). Except for the central sulcus, the same regions showed changes in EC, but not in FEC patients. Of the 97 self-reported responders, 23% and 27% experienced extreme fatigue and long-term cognitive complaints, respectively, which were not associated with metabolic changes.ConclusionBoth hyper- and hypometabolism were observed after chemotherapy for breast cancer. Combined with earlier findings, this study could support inflammatory mechanisms resulting in relative hypermetabolism, mainly in the parietal/occipital cortices. As early metabolic changes did not precede long-term complaints, further research is necessary to identify vulnerable patients.

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“…Although these deficits are mostly subtle, they can have a detrimental effect on the patient's daily life [9]. However, the underlying mechanisms remain largely under investigation [10].…”

Section: Introductionmentioning

confidence: 99%

Neuroinflammation as potential precursor of leukoencephalopathy in early-stage breast cancer patients: A cross-sectional PET-MRI study

et al. 2022

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Background: Although chemotherapy-induced leukoencephalopathy has been described in case and cohort studies, literature remains inconclusive about its prevalence and mechanisms. Therefore, we investigated the presence of leukoencephalopathy after multiagent chemotherapy in women treated for breast cancer and potential underlying neuroinflammatory processes. Methods: In this exploratory study, 15 chemotherapy-treated and 15 age-matched chemotherapy-naïve patients with early-stage breast cancer, as well as 15 healthy controls underwent simultaneous PET-MR neuroimaging, including T1-weighted MPRAGE, T2-weighted FLAIR and dynamic PET with the 18-kDA translocator protein (TSPO) radioligand [ 18 F]DPA-714. Total and regional (juxtacortical, periventricular, deep white matter and infratentorial) lesion burden were compared between the groups with one-way ANOVA. With paired t-tests, [ 18 F] DPA-714 volume of distribution [V T , including partial volume correction (PVC)] in lesioned and normal appearing white matter (NAWM) were compared within subjects, to investigate inflammation. Finally, two general linear models were used to examine the predictive values of neurofilament light-chain (NfL) serum levels on (1) total lesion burden or (2) PVC [ 18 F]DPA-714 V T of lesions showing elevated inflammation. Results: No significant differences were found in total or localized lesion burden. However, significantly higher (20-45%) TSPO uptake was observed in juxtacortical lesions (p ≤ 0.008, t ≥ 3.90) compared to NAWM in both cancer groups, but only persisted for chemotherapy-treated patients after PVC (p = 0.005, t = 4.30). NfL serum levels were not associated with total lesion volume or tracer uptake in juxtacortical lesions. Conclusion: This multimodal neuroimaging study suggests that neuroinflammatory processes could be involved in the development of juxtacortical, but not periventricular or deep white matter, leukoencephalopathy shortly after chemotherapy for early-stage breast cancer.

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Blood and neuroimaging biomarkers of cognitive sequelae in breast cancer patients throughout chemotherapy: A systematic review

Cited by 11 publications

References 73 publications

Characterizing Early Changes in Quality of Life in Young Women With Breast Cancer

Characterizing Early Changes in Quality of Life in Young Women With Breast Cancer

Cerebral glucose changes after chemotherapy and their relation to long-term cognitive complaints and fatigue

Neuroinflammation as potential precursor of leukoencephalopathy in early-stage breast cancer patients: A cross-sectional PET-MRI study

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