Radiation Therapy Before Surgery in Treating Patients With Hormone Receptor Positive, HER2 Negative Breast Cancer

Study Overview
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Brief Summary
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This phase II trial studies how well radiation therapy before surgery works in treating patients with hormone receptor positive, HER2 negative breast cancer. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the change in percent tumor-infiltrating lymphocytes (TIL) as a continuous variable before and after preoperative boost radiotherapy (RT) in hormone receptor (HR)+/human epidermal growth factor receptor2 (HER2)- breast cancers. SECONDARY OBJECTIVES: I. To evaluate the safety of preoperative boost RT administered to patients with HR+/HER2- breast cancer. EXPLORATORY OBJECTIVES: I. To assess the mechanisms of cell death induced by preoperative boost RT. II. To assess immunologic and molecular responses to preoperative boost RT. III. To assess the correlations between immune markers, cell death markers, and their changes during treatment. IV. To determine if magnetic resonance imaging (MRI) can be used to predict breast tumor response to neoadjuvant radiation. OUTLINE: Patients undergo boost radiation therapy 6-8 days before breast surgery. After surgery, patients continue to receive standard of care radiation therapy. After completion of study treatment, patients are followed up at 6 months.

Official Title
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PRECISE: Preoperative Radiotherapy to Elicit Critical Immune Stimulating Effects

Conditions
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Estrogen Receptor Positive, HER2/Neu Negative, Invasive Breast Carcinoma, Progesterone Receptor Positive

Intervention / Treatment
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* Radiation: Radiation Therapy
* Procedure: Therapeutic Conventional Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion: Age >/=18 years at time of study entry Histologically confirmed HR+/HER2- (according to American Society of Clinical Oncology/College of American Pathologists guidelines) invasive carcinoma of the breast Presence of a clip in the primary breast cancer Biopsy-amenable residual disease in the breast measuring >/= 1cm in at least one dimension on ultrasound cm in at least one dimension on ultrasound Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Signed written informed consent Planned for multidisciplinary evaluation by a Breast Surgical Oncologist and Breast Radiation Oncologist. For patients undergoing mastectomy and desirous of reconstruction or those undergoing breast conservation in whom oncoplastic local tissue rearrangement or reduction mammoplasty is being considered, this multidisciplinary evaluation will also include a plastic surgeon. Exclusion: Women who are pregnant or breast-feeding Contraindication to receive radiotherapy

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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (radiation therapy, surgery)<br>Patients undergo boost radiation therapy 6-8 days before breast surgery. After surgery, patients continue to receive standard of care radiation therapy. | Radiation: Radiation Therapy<br>* Undergo radiation therapy<br>* Other names: Therapy, Radiation;Procedure: Therapeutic Conventional Surgery<br>* Undergo breast surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Change in Percent of Tumor-Infiltrating Lymphocytes (TIL) | With 20 patients, a 95% confidence interval for the mean difference between TIL measurements would extend 0.44*s units from the mean (where s is the standard deviation of the TIL differences). If the differences are not normally distributed, researchers will report the median difference along with appropriate 95% confidence intervals. Appropriate graphs used to visualize the data. | 6 to 8 days after preoperative radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delay Rate of Surgery Following Boost RT | Delay rate defined as the proportion of patients experiencing a > 4 week interval between boost RT and surgery. The method of Thall, Simon, and Estey employed to perform interim delay rate monitoring. | 4 weeks after boost RT | 
| Tumor Changes between pre and post boost | For tumor measures, descriptive statistics including plots, tabulations, mean, median, and standard deviations will be used to summarize data. Differences and/or percentage changes will be calculated between pre- and post- therapy samples from each patient and described as continuous measures by using paired t-tests will be explored to evaluate the changes in markers pre- and post-boost therapy. Scatter plots will be used to visualize how correlated between changes in immune markers and extent of tumor cell apoptosis, and the Spearman correlation coefficients will be calculated to evaluate the association between changes in immune markers and extent of tumor cell death markers. | Up to 4 weeks after surgery | 
| Toxicity calculated using the CTCAE v4.0 | Toxicity and cosmesis will be calculated and reported, to enable comparisons to other published reports of breast cancer-related toxicity using the CTCAE v4.0. | 6 months after adjuvant RT | 
| Changes in dynamic contrast enhanced (DCE) | Changes in DCE, internal texture, ADC values, z-spectrum asymmetry on CEST measures will be assessed between the simulation MRI and the MRI obtained following radiation boost. | 4 weeks after surgery |