Prognostic Indicators for Radiation-induced Breast Fibrosis

Study Overview
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Brief Summary
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To study the inflammatory response during and after radiotherapy, especially by measuring the concentration of an enzyme called autotaxin and its product LPA in the blood plasma.

Detailed Description
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To study the inflammatory response during and after radiotherapy, especially by measuring the concentration of an enzyme called autotaxin and its product LPA in the blood plasma. Autotaxin and LPA cause fibrosis in other situation, but they have not been tested in radiation-induced fibrosis. We will determine if the duration and magnitude of the autotaxin and LPA responses are prognostic for the 15-28% of patients who will develop fibrosis. This fibrosis will be detected by ultrasound and a novel application of elastography, which should provide much earlier and quantifiable fibrotic changes compared to conventional physical examination.

Official Title
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Identifying Prognostic Indicators for the Development of Radiation-induced Breast Fibrosis

Conditions
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Breast Cancer

Intervention / Treatment
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* Radiation: Breast Cancer Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female participants capable of giving informed consent, or if appropriate, participants having an acceptable individual capable of giving consent on the participant's behalf Post-menopausal. Treatment with breast conserving surgery. Intended adjuvant whole breast radiotherapy dose to a dose of 40-42.5 Gy in 15-16 fractions. Luminal A subtype as determined by clinipathologic factors (ER/PR positive, Her-2 negative, low Ki-67 or low OncotypeDx recurrence score Exclusion Criteria: Women who have smoked within the last 5 years Patients requiring adjuvant chemotherapy. Requirement for regional nodal radiotherapy. Requirement for tumour bed boost. Breast implants Patients to be treated with partial breast irradiation.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Women undergoing radiation treatment after lumpectomy for breast cancer.<br>There is no specific study intervention being used. Samples will be collected from participants undergoing standard of care radiotherapy at pre-specified timepoints. | Radiation: Breast Cancer Radiotherapy<br>* 4000-4250 cGy in 15-16 daily fractions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of the ATX-LPA (ATX) inflammatory response to standard RT for breast cancer as a prognostic marker for RT-induced fibrosis. | Measurement of longitudinal changes in plasma ATX in the irradiated breast. | Samples will be collected four times during RT treatment (3-4 weeks) and once yearly during follow-up (4 years) | 
| Measurement of the ATX-LPA-inflammatory (LPA) response to standard RT for breast cancer as a prognostic marker for RT-induced fibrosis. | Measurement of longitudinal changes in plasma LPA in the irradiated breast. | Samples will be collected four times during RT treatment (3-4 weeks) and once yearly during follow-up (4 years) | 
| Measurement of the ATX-LPA-inflammatory (cytokines) response to standard RT for breast cancer as a prognostic marker for RT-induced fibrosis. | Measurement of longitudinal changes in plasma cytokines in the irradiated breast. | Samples will be collected four times during RT treatment (3-4 weeks) and once yearly during follow-up (4 years) | 
| Measurement of the ATX-LPA-inflammatory (chemokines) response to standard RT for breast cancer as a prognostic marker for RT-induced fibrosis. | Measurement of longitudinal changes in plasma chemokines in the irradiated breast. | Samples will be collected four times during RT treatment (3-4 weeks) and once yearly during follow-up (4 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Structural changes in the irradiated breast and the non-irradiated breast | The ultrasound procedure will provide a 3D analysis of the breast structure as well as a measurement of breast elasticity. Fibrotic changes in the breast will be measured by combining the 3D analysis and breast elasticity indices (median (kPa), IQR (kPA) and IQR/median (%)) | 3, 6, 12, 24 and 48 months after RT | 
| Acute Radiotherapy Toxicity | Radiotherapy associated toxicities will be assessed per CTCAE v5.0 by the study investigators. | Throughout the duration of the study, a total of 4 years . |