A prospective longitudinal study of cancer-related fatigue in patients undergoing breast-conserving surgery and radiation with or without chemotherapy for breast cancer.

9122 Background: We prospectively evaluated risk factors for persistent cancer-related fatigue in women with breast cancer undergoing lumpectomy with or without chemotherapy (CTX) prior to whole breast radiotherapy (XRT). We assessed the potential role of inflammatory mediators, demographic characteristics, and treatment history including CTX. Methods: Following lumpectomy, 60 women received a definitive course of whole breast XRT (50 Gy plus a 10 Gy boost). Prior to XRT, at week 6 of XRT, and 6 weeks post XRT, subjects completed the Multidimensional Fatigue Inventory (MFI) and underwent blood draws for inflammatory mediators (protein and mRNA). Results: Independent multivariate analyses of clinical and demographic factors revealed that CTX (p<.001) , given neoadjuvantly or adjuvantly, and age <50 (p=.03) were significant predictors of higher fatigue scores post XRT. Mean MFI scores in patients treated with CTX (n=24) were 20 points higher than patients not treated with CTX (p<.001) with a clinically meaningful difference in scores being 10 points on the MFI. Gene ontology analysis of differentially expressed genes indicated increased activation of genes involved in immune and inflammatory responses in fatigued vs. non-fatigued patients (p<.001). Of the inflammatory mediators, plasma IL-6 prior to XRT was the strongest predictor of post XRT fatigue (p=.02). Moreover, plasma IL-6 concentrations prior to XRT were significantly higher in patients who received CTX (mean 4.96 vs. 2.53, p=.01). Patients who received CTX also had significantly higher levels of NF Kappa B DNA binding 6 weeks post XRT (p<.001), and transcription factor binding analysis revealed a greater representation of genes with the NF Kappa B DNA binding motif in fatigued vs. non-fatigued patients (p =.05). Conclusions: Collectively, these data suggest an interaction between CTX and XRT leading to inflammation and fatigue several weeks post XRT. This relationship was independent of whether CTX was given pre or post-operatively. Treatments targeting inflammation before XRT may reduce fatigue post therapy, particularly in patients previously treated with CTX.

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The association between cancer-related fatigue and diabetes from pre-chemotherapy to 6-months post-chemotherapy

10.21203/rs.3.rs-220601/v1 ◽

2021 ◽

Author(s):

Amber Kleckner ◽

Ian R. Kleckner ◽

Eva Culakova ◽

Michelle Shayne ◽

Elizabeth K. Belcher ◽

...

Keyword(s):

Breast Cancer ◽

Repeated Measures ◽

Diabetes Management ◽

Menopausal Status ◽

Secondary Analysis ◽

Prospective Longitudinal Study ◽

Cancer Related Fatigue ◽

Diabetes Status ◽

Prospective Longitudinal ◽

The Impact

Abstract Purpose To quantify the impact of diabetes on the trajectory of cancer-related fatigue (CRF) from pre-chemotherapy to 6 months post-chemotherapy for patients with breast cancer compared to non-cancer controls.Methods This was a secondary analysis from a nationwide prospective longitudinal study of female patients with breast cancer undergoing chemotherapy and age-matched women without cancer (controls). CRF was measured using the Multidimensional Fatigue Symptom Inventory (MFSI) pre-, post-, and 6-months post-chemotherapy in patients; controls were assessed at equivalent time points. Diabetes status was obtained at baseline. Repeated measures mixed models estimated the association between CRF and diabetes controlling for cancer (y/n), body mass index, exercise and smoking habits, baseline anxiety and depressive symptoms, menopausal status, marital status, race, and education.Results A total of 439 patients and 235 controls (age: 52.8±10.5 years) had available data on diabetes status. Diabetes was twice as prevalent among patients as controls (11.6% vs. 6.8%). Patients had worse fatigue than controls throughout treatment (p<0.001). Diabetes was associated with worse CRF with a clinically meaningful difference of 4.7±1.7 points on the fatigue measure in all participants (p=0.009) and patients alone (p=0.030). For MFSI subdomains, diabetes was associated with worse general (p=0.002), physical (p=0.005), and mental fatigue (p=0.025) but not worse emotional fatigue or vigor (p>0.14) among patients. Conclusions Diabetes was twice as prevalent in women with breast cancer compared to controls, and diabetes was associated with more severe CRF in patients before and after chemotherapy and at 6 months post-chemotherapy. Interventions that address diabetes management may also help address CRF during chemotherapy treatment

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A prospective study of cancer-related fatigue in women undergoing radiotherapy for breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.27_suppl.110 ◽

2011 ◽

Vol 29 (27_suppl) ◽

pp. 110-110

Author(s):

M. A. Torres ◽

T. Liu ◽

H. Chen ◽

K. D. Godette ◽

L. J. Stapleford ◽

...

Keyword(s):

Breast Cancer ◽

Inflammatory Mediators ◽

Tissue Characterization ◽

Breast Radiotherapy ◽

Ultrasound Tissue Characterization ◽

Cancer Related Fatigue ◽

Validated Questionnaire ◽

Whole Breast Radiotherapy ◽

Potential Risk Factors ◽

A Prospective Study

110 Background: To investigate potential risk factors for cancer-related fatigue in women with breast cancer undergoing whole-breast radiotherapy (RT), we assessed the contribution of chemotherapy (CTX), RT-induced epidermal thickening, and inflammatory mediators to post RT fatigue. Methods: Following lumpectomy, 30 women received whole breast RT (50 Gy plus a 10 Gy boost). Prior to RT, at week 6 of RT, and 6 weeks post RT, subjects completed a validated questionnaire assessing fatigue (Multidimensional Fatigue Inventory [MFI-20]). At the above visits, patients underwent blood sampling for inflammatory mediators. In addition, breast epidermal thickness was measured using ultrasound tissue characterization. Results: Fatigue scores in the sample as a whole did not increase during RT. Independent multivariate analyses of clinical and demographic factors revealed that prior CTX (p<.001) and age <50 (p=.03) were significant predictors of higher post RT fatigue scores. Before, during, and after RT, CTX-treated patients had significantly higher mean fatigue scores than non-CTX-treated subjects. For example, mean MFI scores post RT in patients previously treated with CTX (n=15) were 28 points higher than patients not treated with CTX (mean 61 vs. 33, p<.001), with a clinically meaningful difference being 10 points. Race, cancer stage, and epidermal thickening (defined as a 50% increase over baseline during or after RT, n=17) did not predict higher post RT fatigue scores. Of the inflammatory mediators, plasma IL-6 prior to RT was the strongest predictor of post RT fatigue (p=.02). In addition, plasma IL-6 concentrations prior to RT were significantly higher in patients who received CTX versus those who did not (mean 5.0 vs. 2.5, p=.01). IL-6 prior to RT was also significantly correlated with RT-induced epidermal thickening (p=.04). Conclusions: Our study suggests that CTX-induced inflammation, measured by plasma IL-6, is independently associated with the development of fatigue as well as epidermal thickening in women undergoing breast RT. Treatments targeting inflammation before RT may reduce both fatigue and epidermal thickening post RT, particularly in patients who have been previously been treated with CTX.

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An Evaluation of DNA Methyltransferase 1 (DNMT1) Single Nucleotide Polymorphisms and Chemotherapy-Associated Cognitive Impairment: A Prospective, Longitudinal Study

Scientific Reports ◽

10.1038/s41598-019-51203-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Alexandre Chan ◽

Angie Yeo ◽

Maung Shwe ◽

Chia Jie Tan ◽

Koon Mian Foo ◽

...

Keyword(s):

Breast Cancer ◽

Cognitive Impairment ◽

Cognitive Function ◽

Cancer Patients ◽

Dna Methyltransferase ◽

Dna Methyltransferases ◽

Breast Cancer Patients ◽

Prospective Longitudinal Study ◽

Cognitive Domains ◽

Prospective Longitudinal

Abstract Strong evidence suggests that genetic variations in DNA methyltransferases (DNMTs) may alter the downstream expression and DNA methylation patterns of neuronal genes and influence cognition. This study investigates the association between a DNMT1 polymorphism, rs2162560, and chemotherapy-associated cognitive impairment (CACI) in a cohort of breast cancer patients. This is a prospective, longitudinal cohort study. From 2011 to 2017, 351 early-stage breast cancer patients receiving chemotherapy were assessed at baseline, the midpoint, and the end of chemotherapy. DNA was extracted from whole blood, and genotyping was performed using Sanger sequencing. Patients’ self-perceived cognitive function and cognitive performance were assessed at three different time points using FACT-Cog (v.3) and a neuropsychological battery, respectively. The association between DNMT1 rs2162560 and cognitive function was evaluated using logistic regression analyses. Overall, 33.3% of the patients reported impairment relative to baseline in one or more cognitive domains. Cognitive impairment was observed in various objective cognitive domains, with incidences ranging from 7.2% to 36.9%. The DNMT1 rs2162560 A allele was observed in 21.8% of patients and this was associated with lower odds of self-reported cognitive decline in the concentration (OR = 0.45, 95% CI: 0.25–0.82, P = 0.01) and functional interference (OR = 0.48, 95% CI: 0.24–0.95, P = 0.03) domains. No significant association was observed between DNMT1 rs2162560 and objective cognitive impairment. This is the first study to show a significant association between the DNMT1 rs2162560 polymorphism and CACI. Our data suggest that epigenetic processes could contribute to CACI, and further studies are needed to validate these findings.

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

Journal of Clinical Oncology ◽

10.1200/jco.2016.68.5826 ◽

2017 ◽

Vol 35 (5) ◽

pp. 506-514 ◽

Cited By ~ 94

Author(s):

Michelle C. Janelsins ◽

Charles E. Heckler ◽

Luke J. Peppone ◽

Charles Kamen ◽

Karen M. Mustian ◽

...

Keyword(s):

Breast Cancer ◽

Cognitive Impairment ◽

Cognitive Function ◽

Reading Ability ◽

Menopausal Status ◽

Prospective Longitudinal Study ◽

Cognitive Difficulties ◽

Community Oncology ◽

Prospective Longitudinal

Purpose Cancer-related cognitive impairment is an important problem for patients with breast cancer, yet its trajectory is not fully understood. Some previous cancer-related cognitive impairment research is limited by heterogeneous populations, small samples, lack of prechemotherapy and longitudinal assessments, use of normative data, and lack of generalizability. We addressed these limitations in a large prospective, longitudinal, nationwide study. Patients and Methods Patients with breast cancer from community oncology clinics and age-matched noncancer controls completed the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) at prechemotherapy and postchemotherapy and at a 6-month follow-up as an a priori exploratory aim. Longitudinal models compared FACT-Cog scores between patients and controls at the three assessments and adjusted for age, education, race, menopausal status, and baseline reading ability, anxiety, and depressive symptoms. A minimal clinically important difference cutoff determined percentages of impairment over time. Results Of patients, 581 patients with breast cancer (mean age, 53 years; 48% anthracycline-based regimens) and 364 controls (mean age, 53 years) were assessed. Patients reported significantly greater cognitive difficulties on the FACT-Cog total score and four subscales from prechemotherapy to postchemotherapy compared with controls as well as from prechemotherapy to 6-month follow-up (all P < .001). Increased baseline anxiety, depression, and decreased cognitive reserve were significantly associated with lower FACT-Cog total scores. Treatment regimen, hormone, or radiation therapy was not significantly associated with FACT-Cog total scores in patients from postchemotherapy to 6-month follow-up. Patients were more likely to report a clinically significant decline in self-reported cognitive function than were controls from prechemotherapy to postchemotherapy (45.2% v 10.4%) and from prechemotherapy to 6-month follow-up (36.5% v 13.6%). Conclusion Patients with breast cancer who were treated in community oncology clinics report substantially more cognitive difficulties up to 6 months after treatment with chemotherapy than do age-matched noncancer controls.

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