scholarly journals Impact of Physical Activity on Oxidative Stress Markers in Patients with Metastatic Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Lidia Delrieu ◽  
Marina Touillaud ◽  
Olivia Pérol ◽  
Magali Morelle ◽  
Agnès Martin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Physical Activity ◽  
Enzyme Activity ◽  
Metastatic Breast Cancer ◽  
Tumor Progression ◽  
Plasma Concentrations ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Oxidative Stress Biomarkers

Purpose. Regular physical activity (PA) can affect oxidative stress, known to be involved in carcinogenesis. The objective of this study was to evaluate the associations between a six-month PA intervention and oxidative stress biomarkers, PA, and clinical outcomes in patients with metastatic breast cancer. Methods. Forty-nine newly diagnosed patients with metastatic breast cancer were recruited for a single-arm, unsupervised, and personalized six-month walking intervention with activity tracker. PA level and PA fitness, plasma concentrations of DNA oxidation (8OhdG), lipid peroxidation (MDA), and protein oxidation (AOPP), plasma activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase, plasma and leucocyte activities of myeloperoxidase (MPO) and NADPH oxidase (NOX), and clinical markers of tumor progression (RECIST criteria) were measured at baseline and after the six-month intervention. Results. GPX activity (+17%) and MDA (+9%) significantly increased between baseline and the end of the intervention. Changes in PA level and fitness were significantly positively correlated with changes in plasma GPX and significantly negatively with changes in NOX in the leucocytes. Plasma MDA was significantly higher (+20%) whereas plasma AOPP was lower (-46%) for patients with tumor progression or that died during the six months as compared to patients without progression. Conclusion. A six-month PA intervention may be potentially beneficial in metastatic breast cancer patients for enhancing antioxidant enzyme activity and decreasing prooxidant enzyme activity. Moreover, AOPP and MDA could also be favorable and unfavorable biomarkers, respectively, since they are associated with disease progression and fitness level in this population. This trial is registered with NCT number: NCT03148886.

Clinical Implications of CYP2D6 Genotypes Predictive of Tamoxifen Pharmacokinetics in Metastatic Breast Cancer

2007 ◽  
Vol 25 (25) ◽  
pp. 3837-3845 ◽  
Author(s):  
Hyeong-Seok Lim ◽  
Han Ju Lee ◽  
Keun Seok Lee ◽  
Eun Sook Lee ◽  
In-Jin Jang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Steady State ◽  
Clinical Outcome ◽  
Plasma Concentrations ◽  
Metastatic Breast ◽  
Pregnane X Receptor ◽  
Cyp2d6 Genotype ◽  
Breast Cancer Patients ◽  
State Plasma

Purpose The CYP3A and CYP2D6 enzymes play a major role in converting tamoxifen to its active metabolites. CYP3A is a highly inducible enzyme, regulated mainly by pregnane X receptor (PXR). This study assessed the association between genetic polymorphisms of CYP2D6 and PXR, and tamoxifen pharmacokinetics (PK) and clinical outcomes in patients with breast cancer. Patients and Methods Plasma concentrations of tamoxifen and its metabolites were measured. Common alleles of CYP2D6 and PXR were identified in 202 patients treated with tamoxifen 20 mg daily for more than 8 weeks. Twelve of the 202 patients and an additional nine patients with metastatic breast cancer receiving tamoxifen were assessed for clinical outcome in correlation with genotypes. Results Patients carrying CYP2D6*10/*10 (n = 49) demonstrated significantly lower steady-state plasma concentrations of 4-hydroxy-N-desmethyltamoxifen and 4-hydroxytamoxifen than did those with other genotypes (n = 153; 4-hydroxy-N-desmethyltamoxifen: 7.9 v 18.9 ng/mL, P < .0001; 4-hydroxytamoxifen: 1.5 v 2.6 ng/mL, P < .0001), whereas no difference by PXR genotypes was found. CYP2D6*10/*10 was significantly more frequent among nonresponders with MBC (100% v 50%, P = .0186). In Cox proportional hazard analysis, CYP2D6 genotype and number of disease sites were significant factors affecting time to progression (TTP). The median TTP for patients receiving tamoxifen was shorter in those carrying CYP2D6*10/*10 than for others (5.0 v 21.8 months, P = .0032) Conclusion CYP2D6*10/*10 is associated with lower steady-state plasma concentrations of active tamoxifen metabolites, which could possibly influence the clinical outcome by tamoxifen in Asian breast cancer patients.

scholarly journals Human G-MDSCs are neutrophils at distinct maturation stages promoting tumor growth in breast cancer

2020 ◽  
Vol 3 (11) ◽  
pp. e202000893
Author(s):  
Meliha Mehmeti-Ajradini ◽  
Caroline Bergenfelz ◽  
Anna-Maria Larsson ◽  
Robert Carlsson ◽  
Kristian Riesbeck ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Immune Cell ◽  
Human Tumor ◽  
Metastatic Breast ◽  
Suppressor Cells ◽  
Breast Cancer Patients ◽  
Maturation Stages

Myeloid-derived suppressor cells (MDSCs) are known to contribute to immune evasion in cancer. However, the function of the human granulocytic (G)-MDSC subset during tumor progression is largely unknown, and there are no established markers for their identification in human tumor specimens. Using gene expression profiling, mass cytometry, and tumor microarrays, we here demonstrate that human G-MDSCs occur as neutrophils at distinct maturation stages, with a disease-specific profile. G-MDSCs derived from patients with metastatic breast cancer and malignant melanoma display a unique immature neutrophil profile, that is more similar to healthy donor neutrophils than to G-MDSCs from sepsis patients. Finally, we show that primary G-MDSCs from metastatic breast cancer patients co-transplanted with breast cancer cells, promote tumor growth, and affect vessel formation, leading to myeloid immune cell exclusion. Our findings reveal a role for human G-MDSC in tumor progression and have clinical implications also for targeted immunotherapy.

Oxidative stress status in metastatic breast cancer patients receiving palliative chemotherapy and its impact on survival rates

2011 ◽  
Vol 46 (1) ◽  
pp. 2-10 ◽  
Author(s):  
Laura Vera-Ramirez ◽  
Pedro Sanchez-Rovira ◽  
M. Carmen Ramirez-Tortosa ◽  
Cesar L. Ramirez-Tortosa ◽  
Sergio Granados-Principal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Palliative Chemotherapy ◽  
Survival Rates ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Oxidative Stress Status ◽  
Impact On Survival

scholarly journals Sarcopenia and serum biomarkers of oxidative stress after a 6-month physical activity intervention in women with metastatic breast cancer: results from the ABLE feasibility trial

2021 ◽  
Author(s):  
Lidia Delrieu ◽  
Agnès Martin ◽  
Marina Touillaud ◽  
Olivia Pérol ◽  
Magali Morelle ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Physical Activity ◽  
Metastatic Breast Cancer ◽  
Muscle Mass ◽  
Physical Activity Intervention ◽  
Metastatic Breast ◽  
Lumbar Vertebra ◽  
Muscle Quality ◽  
Feasibility Trial

Abstract Purpose Sarcopenia has been identified as an important prognostic factor for patients with cancer. This study aimed at exploring the potential associations between a 6-month physical activity intervention and muscle characteristics, sarcopenia, oxidative stress and toxicities in patients with metastatic breast cancer. Methods Women newly diagnosed with metastatic breast cancer (N = 49) participated in an unsupervised, personalized, 6-month physical activity intervention with activity tracker. Computerized tomography images at the third lumbar vertebra were analysed at baseline, three months and six months to assess sarcopenia (muscle mass index < 40 cm2/m2) and muscle quality (poor if muscle attenuation < 37.8 Hounsfield Units). Oxidative markers included plasma antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase activities), prooxidant enzymes (NADPH oxidase and myeloperoxidase activities) and oxidative stress damage markers (advanced oxidation protein products, malondialdehyde (MDA) and DNA oxidation. Results At baseline 53% (mean age 55 years (SD 10.41)) were sarcopenic and 75% had poor muscle quality. Muscle cross sectional area, skeletal muscle radiodensity, lean body mass remained constant over the six months (p = 0.75, p = 0.07 and p = 0.75 respectively), but differed significantly between sarcopenic and non-sarcopenic patients at baseline and 6-months. Sarcopenic patients at baseline were more likely to have an increase of MDA (p = 0.02) at 6 months. Being sarcopenic during at least one moment during the 6-month study was associated with a higher risk of developing severe toxicities (grade > 2) (p = 0.02). Conclusions This study suggests potential benefits of physical activity for maintenance of muscle mass. Sarcopenia can alter many parameters and disturb the pro and antioxidant balance.

Effect of tailored and supervised therapeutic exercise in metastatic breast cancer patients: A prospective study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13075-e13075
Author(s):  
Sofía Ruíz ◽  
Bella Pajares ◽  
Maria-Jose Bermejo-Perez ◽  
Cristina Roldán Jiménez ◽  
Antonio Cuesta Vargas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Physical Activity ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Cancer Related Fatigue ◽  
A Prospective Study

e13075 Background: The safety, feasibility and benefit of physical activity is robust in adjuvant breast cancer, but as far as we know, there is little information on the feasibility and benefit of exercise in women with advanced breast cancer. The objective of our study is to analyze the feasibility and impact on fatigue, quality of life and functionality of an individualized, prospective and supervised exercise program in a group of patients with metastatic breast cancer. Methods: A prospective study on 30 metastatic breast cancer patients who were recruited as volunteers between February 2018 and April 2019 by Medical Oncologists from the Medical Oncology Unit at University Clinical Hospital Virgen de la Victoria (Malaga, Spain). Participants included in this study were patients aged between 34 and 71 years old and all had metastatic breast cancer, not amenable to curative treatment. The intervention was a twelve-week Therapeutic Exercise and Education Programme delivered by a physiotherapist. The intervention was preceded by a physical assessment of the musculoskeletal system. The outcomes were cancer-related fatigue, quality of life and functional outcomes (patient- reported and other measured by investigators). Results: Of the 30 patients initially recruited, only 11 of them completed the program with an attendance greater or equal to 17 sessions (75% of assistance). Most of patients who dropped (19), did it because of personal matters, not related to disease progression. Regarding patients who completed the completion of physical activity program (n = 11), the majority were treated on first line of treatment with hormonal receptors positive tumors and bone metastasis. After the intervention, no major changes were observed in cancer-related fatigue, quality of life and several patients-reported outcomes, although an improvement in functionality was observed, in investigator-measured parameters (30-STS and adapted burpees). Conclusions: Our study shows that a supervised and individualized tailored physical activity program in metastatic breast cancer patients is safe and feasible, although more studies are needed to analyse its impact on improving functional parameters, fatigue and quality of life.

Phase I Clinical Trial of Alitretinoin and Tamoxifen in Breast Cancer Patients: Toxicity, Pharmacokinetic, and Biomarker Evaluations

2001 ◽  
Vol 19 (10) ◽  
pp. 2754-2763 ◽  
Author(s):  
Julia A. Lawrence ◽  
Peter C. Adamson ◽  
Rafael Caruso ◽  
Catherine Chow ◽  
David Kleiner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Single Agent ◽  
Plasma Concentrations ◽  
Density Lipoprotein ◽  
Metastatic Breast ◽  
Tamoxifen Therapy ◽  
Breast Cancer Patients ◽  
Grade 3 ◽  
Mib 1

PURPOSE: To determine the overall and dose-limiting toxicities (DLTs) of alitretinoin (9-cis-retinoic acid) in combination with tamoxifen and the pharmacokinetics of alitretinoin alone and when combined with tamoxifen in patients with metastatic breast cancer. The effect of tamoxifen and alitretinoin on MIB-1, a marker of proliferation, in unaffected breast tissue was explored. PATIENTS AND METHODS: Eligible patients had metastatic breast cancer. Previous tamoxifen therapy was allowed. Planned dose levels for alitretinoin ranged from 50 to 140 mg/m2/d with 20 mg/d tamoxifen in all patients after 4 weeks of alitretinoin as a single agent. Plasma concentrations of alitretinoin and retinol were measured at baseline and after 1, 2, and 3 months. Breast core biopsies were obtained at baseline and after 2 months of therapy. RESULTS: Twelve patients with metastatic breast cancer received a total of 86 cycles of therapy. At 90 mg/m2/d, three of five patients experienced a DLT: grade 3 headache, grade 3 hypercalcemia, and grade 3 noncardiogenic pulmonary edema. At 70 mg/m2/d, one of six patients experienced a DLT (headache), and this level was considered the maximal tolerated dose in this study. Three toxicities occurred that had not been reported previously with alitretinoin: an asymptomatic delay in dark adaptation, a marked decrease in high-density lipoprotein cholesterol, and the occurrence of enthesopathy. Two of the nine assessable patients had a durable clinical response: one partial response and stable disease for 18 months and one complete response in continuous remission for 48+ months. Both responding patients were estrogen receptor–positive and had had previous tamoxifen therapy. There was a high degree of interpatient variability of plasma alitretinoin concentrations, although a significant decline in alitretinoin plasma levels over time was observed. MIB-1 scores declined in four of the eight paired breast specimens obtained. CONCLUSION: The combination of tamoxifen and alitretinoin is well tolerated and has antitumor activity in metastatic breast cancer. The recommended phase II dose is 70 mg/m2/d with 20 mg/d tamoxifen.

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