Histamine and Bone Pain Association in Participants With Breast Cancer Metastatic in the Bone

Study Overview
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Brief Summary
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This trial studies histamine and bone pain association in participants with breast cancer that has spread to the bone. Studying histamine levels in samples of blood from participants with breast cancer in the laboratory may help doctors learn more about reducing cancer bone pain and preventing further bone metastasis.

Detailed Description
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PRIMARY OBJECTIVES: I. To correlate levels of histamine in plasma with pain scores in patients with bone metastases from breast cancer that have or have not been treated with palliative radiotherapy. SECONDARY OBJECTIVES: I. To perform exploratory studies with additional markers not mentioned, including calcitonin gene-related peptide (CGRP), stem cell factor (SCF), angiotensin II (Ang II) substance P, angiotensin 1-7 (Ang1-7), may be performed at the investigator's discretion. II. To perform next generation ribonucleic acid (RNA) sequences using the whole blood to determine whether histamine system is involved in the development of cancer-induced bone pain (CIBP). III. To assess the impact of pain response after radiotherapy on bone structural properties such as bone mineral density and cortical thickness, and patient quality of life, physical and psychological function. OUTLINE: Participants undergo collection of blood samples for histamine level analysis via enzyme-linked immunosorbent assay (ELISA). After completion of study, participants are followed up at 1, 3, and 6 months.

Official Title
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The Role of Histamine in Breast Cancer Bone Pain

Conditions
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Bone Pain, Breast Carcinoma Metastatic in the Bone

Intervention / Treatment
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* Procedure: Biospecimen Collection
* Other: Laboratory Biomarker Analysis
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Breast cancer patients with radiographic evidence of bone metastases (by plain film, computed tomography [CT], magnetic resonance imaging [MRI], positron emission tomography [PET] or bone scan) within 8 weeks of registration Weight bearing sites: pelvis (excluding pubis), femur, sacrum and/or sacroiliac joints, tibia, up to 5 consecutive cervical, thoracic or lumbar vertebral bodies, lumbosacral spine Non-weight bearing sites: up to 3 consecutive ribs, humerus, fibula, radius +/- ulna, clavicle, sternum, scapula, pubis Patients with and without pain related to the radiographically documented metastases are eligible for study Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document Exclusion Criteria: Pregnant women will be excluded

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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 |
| --- | --- |
| Ancillary-Correlative (biospecimen collection)<br>Participants undergo collection of blood samples for histamine level analysis via ELISA. | Procedure: Biospecimen Collection<br>* Undergo collection of blood<br>Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma histamine levels | To correlate levels of histamine in plasma with pain scores (3 groups) in patients with bone metastases from breast cancer that have or have not been treated with palliative radiotherapy, analysis of variance (ANOVA) will be used. The histamine levels will be transformed to satisfy the conditional normality assumption if needed. Linear regression models will be used to relate histamine levels (outcome variable) with the pain groups (covariate of interest). | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calcitonin gene-related peptide (CGRP) | Levels of CGRP will be collected. Statistical analysis will correlate CGRP with pain scores (3 groups) in patients with bone metastases from breast cancer that have or have not been treated with palliative radiotherapy, ANOVA will be used. | Up to 6 months | 
| Stem cell factor (SCF) | Levels of SCF will be collected. Statistical analysis will correlate SCF with pain scores (3 groups) in patients with bone metastases from breast cancer that have or have not been treated with palliative radiotherapy, ANOVA will be used. | Up to 6 months | 
| angiotensin II (Ang II) Substance P | Levels of Ang II will be collected. Statistical analysis will correlate Ang II with pain scores (3 groups) in patients with bone metastases from breast cancer that have or have not been treated with palliative radiotherapy, ANOVA will be used. | Up to 6 months | 
| angiotensin 1-7 (Ang1-7) levels | Levels of Ang 1-7 will be collected. Statistical analysis will correlate Ang 1-7 with pain scores (3 groups) in patients with bone metastases from breast cancer that have or have not been treated with palliative radiotherapy, ANOVA will be used. | Up to 6 months | 
| Histamine system involvement | Will perform next generation ribonucleic acid (RNA) sequences using whole blood to determine whether histamine system is involved in the development of cancer-induced bone pain (CIBP). | Up to 6 months | 
| Change in bone structural properties | The thickness of the cortical bone within the irradiated volume will be measured. | Baseline up to 1 month | 
| Change in patient quality of life | The change in patient quality of life will be assessed by the visual analogue scale (VAS) pain scale. The total score range is 0-10 with higher scores denoting worse outcomes. | Baseline up to 1 month | 
| Change in physical and psychological function | To be measured using the EORTC QLQ-BM22 quality of life questionnaire. It's divided into two categories, giving a single value: symptoms and functions. A high score indicates a high level of symptoms and a high level of functioning. The score range is 22-88. | Baseline up to 1 month |