Identifying Biomarkers for Chronic Pain After Breast Cancer Treatment.

Study Overview
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Brief Summary
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Up to 40% of women experience chronic pain after treatment for breast cancer, and this pain is often very disabling. However, chronic pain after breast cancer remains under-recognised and undertreated. An effective and patient-tailored approach of (chronic) pain after breast cancer indeed requires a thorough knowledge and evaluation of the pain. In daily clinical practice, however, guidelines for a comprehensive diagnosis of pain in cancer patients and survivors are lacking. Further research in this topic is crucial for an efficient, preventive as well as curative, approach of pain after breast cancer. Besides the high prevalence and the important impact of pain in this population, the breast cancer population is also an ideal population to study chronic pain and its natural time course in different stages, since most patients start pain-free, but almost half of them end up with chronic pain. Therefore, this study aims to map biomarkers (both predictive, prognostic and diagnostic) for chronic pain after breast cancer treatment. We will study possible biopsychosocial biomarkers in relation to (chronic) pain and monitor their temporal changes from the moment of diagnosis until 1 year after surgery. The potential biomarkers are situated within the medical imaging of the brain, measurements of pain sensitivity and psychological variables.

Official Title
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sCANsens: Identifying Biomarkers for Chronic Pain After Breast Cancer Treatment

Conditions
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Neoplasm, Breast, Carcinoma Breast, Chronic Pain

Intervention / Treatment
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* Diagnostic Test: Biomarkers


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unilateral breast cancer Pain at enrollment <3/10 on average during the past week First cancer diagnosis Exclusion Criteria: Pre-existing pain conditions major pre-existing neurological disorders No recurrent cancer or metastasis No previous surgery in area

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Breast cancer<br>Breast cancer patients following over time during cancer treatment | Diagnostic Test: Biomarkers<br>* Each intervention is performed at 4 timepoints namely: before surgery, i.e. baseline (T0), 1-3 weeks post-surgery (T1), 3 months post-surgery (T2) and 1 year post-surgery (T4)<br>* Other names: Blood analysis: Cytokine and Brain-Derived Neurotrophic Factor expression measurements, SNPs and CpG methylation detection.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Localisation of pain | Localisation and experience of pain after cancer treatment measured with the Mc Gill Pain Questionnaire Dutch Language Version: Anamnesis questions to localize the pain and the experience of the patient. Assessment at T0: pre-surgery, T1: 1-3 weeks post-surgery, T2: 3 months post-surgery, T3: 1 year post-surgery | Time frame up to 1 year post-surgery | 
| Pain intensity | Visual Analogue Scale included in the Mc Gill Pain Questionnaire is a 100mm horizontal line were the patient is asked to indicate his/her perceived pain intensity at this moment, the minimum and the maximum of the pain. Assessment at T0: pre-surgery, T1: 1-3 weeks post-surgery, T2: 3 months post-surgery, T3: 1 year post-surgery | Time frame up to 1 year post-surgery | 
| Influence of pain on the quality of life | Quality of Life questions included in the Mc Gill Pain Questionnaire: self-report to indicate the impact of pain on quality of life. The higher the score the higher the impact (0-27). Assessment at T0: pre-surgery, T1: 1-3 weeks post-surgery, T2: 3 months post-surgery, T3: 1 year post-surgery | Time frame up to 1 year post-surgery | 
| Severity of pain symptoms | Adjective list of pain symptoms included in the Mc Gill Pain Questionnaire Dutch : Language Version (0-63): Self-report of pain evaluating the sensory intensity, emotional impact and the cognitive evaluation of pain. Each part or dimension of the MPQ is individually scored and a cumulative total score is also recorded. Assessment at T0: pre-surgery, T1: 1-3 weeks post-surgery, T2: 3 months post-surgery, T3: 1 year post-surgery | Time frame up to 1 year post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prognostic value of Pain Catastrophizing | Pain Catastrophizing Scale (0-52) : It is a self-report measure, consisting of 13 items scored from 0 to 4, resulting in a total possible score of 52. The higher the score, the more catastrophizing thoughts are present. | Assessment at T0: pre-surgery, T1: 1-3 weeks post-surgery, T2: 3 months post-surgery, T3: 1 year post-surgery | 
| Prognostic value of Depression, Anxiety and Stress | Depression, Anxiety and Stress Scale (DASS-21) (range 0-132). The Depression, Anxiety and Stress Scale - 21 Items (DASS-21) is a set of three self-report scales designed to measure the emotional states of depression, anxiety and stress | Assessment at T0: pre-surgery, T1: 1-3 weeks post-surgery, T2: 3 months post-surgery, T3: 1 year post-surgery | 
| Prognostic value of Positive and Negative affect | Positive and Negative Affect Schedule (10-50): This scale consists of different words that describe feelings and emotions, it measures positive and negative affect. Lower scores representing lower levels of Positive/Negative Affect and higher scores representing higher levels of Positive/Negative Affect. | Assessment at T0: pre-surgery, T1: 1-3 weeks post-surgery, T2: 3 months post-surgery, T3: 1 year post-surgery | 
| Prognostic value of Resilience | VK+ : This scale gives an indication about the resilience of the patients (0-100). The higher the score, the more resilience is present. | Assessment at T0: pre-surgery, T1: 1-3 weeks post-surgery, T2: 3 months post-surgery, T3: 1 year post-surgery | 
| Prognostic value of hyperalgesia | Cold and hot detection and pain thresholds are measured as the first identified stimulus under increasing stimulus intensities. Thresholds are measured at local places to evaluate primary hyperalgesia and a distant location to assess secondary hyperalgesia. Results are compared with normative data. | Assessment at T0: pre-surgery, T1: 1-3 weeks post-surgery, T2: 3 months post-surgery, T3: 1 year post-surgery | 
| Prognostic value of conditioned pain modulation | 'Test' stimulus and a 'conditioning' stimulus applied is used to assess pain sensitivity to a warmth stimulus pre- and post the noxious conditioning stimulus and the difference is calculated between premeasures and postmeasures. When the second pressure pain threshold (i.e., test stimulus) is similar or lower than the first, dysfunctional inhibitory pain mechanisms are present. | Assessment at T0: pre-surgery, T1: 1-3 weeks post-surgery, T2: 3 months post-surgery, T3: 1 year post-surgery | 
| Prognostic value of temporal summation | Repetitive stimuli are given of which the perceived intensity of the stimulus (first, last and after sensations) is measured by a Numeric Rating Scale. The difference between the first and the last stimuli is calculated in order to determine the temporal summation. Enhanced temporal summation is considered as positive with at least two points of increase on the NRS | Assessment at T0: pre-surgery, T1: 1-3 weeks post-surgery, T2: 3 months post-surgery, T3: 1 year post-surgery | 
| Prognostic value of gray matter differences | T1 acquisition and Voxel-Based Morphometry is used to measure regional differences in gray matter. T2 acquisition is applied for possible co-registration and improving robustness for post-processing pipelines. | Assessment at T0: pre-surgery, T1: 1-3 weeks post-surgery, T2: 3 months post-surgery, T3: 1 year post-surgery | 
| Prognostic value of functional connectivity | Rs-fMRI acquisition is used to measure functional connectivity. | Assessment at T0: pre-surgery, T1: 1-3 weeks post-surgery, T2: 3 months post-surgery, T3: 1 year post-surgery | 
| Prognostic value of Fractional Anisotropy | Diffusion Weighted Imaging acquisition is used to assess differences in fractional anisotropy. T2 acquisition is applied for possible co-registration and improving robustness for post-processing pipelines. | Assessment at T0: pre-surgery, T1: 1-3 weeks post-surgery, T2: 3 months post-surgery, T3: 1 year post-surgery | 
| Prognostic value of the percentage CpG methylation in gene regions of selected cytokine and Brain Derived Neurotrophic Factor genes. | Genes associated with the persistent pain phenotype will be selected using multivariate analysis. CpG methylation is determined using bisulfate CpG pyrosequencing. PyroMark Q24 Analyses software will assess the average methylation of each CpG in the different gene regions of interest and return a percentage (from 0-100% methylation) as a result. | Assessment at T0: pre-surgery, T1: 1-3 weeks post-surgery, T2: 3 months post-surgery, T3: 1 year post-surgery | 
| Prognostic value of cytokine expression | Interested cytokines will be selected using multivariate analyses. Plasma samples will be assessed using a multiplex panel. | Assessment at T0: pre-surgery, T1: 1-3 weeks post-surgery, T2: 3 months post-surgery, T3: 1 year post-surgery | 
| Prognostic value of Brain Derived Neurotrophic factor expression | Measurements of soluble Brain Derived Neurotrophic factor expression is assessed using enzyme-linked immunosorbent assay. | Assessment at T0: pre-surgery, T1: 1-3 weeks post-surgery, T2: 3 months post-surgery, T3: 1 year post-surgery | 
| Prognostic value of single nucleotide polymorphisms (SNPs) | A total of 82 SNPs from 15 cytokine genes and 2 SNPs of brain derived neurotrophic factor will be analysed using a SNP genotyping assay. | Assessment at T0: pre-surgery, T1: 1-3 weeks post-surgery, T2: 3 months post-surgery, T3: 1 year post-surgery |