Radiation Therapy During Surgery in Treating Older Women With Invasive Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation during surgery may be an effective treatment for breast cancer. PURPOSE: This phase II trial is studying how well radiation therapy works in treating older women who are undergoing surgery for invasive breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the feasibility of intraoperative partial breast radiotherapy prior to surgical resection in older women with low-risk early stage primary invasive ductal carcinoma of the breast. Feasibility will be determined by the rate of good/excellent cosmesis, as measured by the Radiation Therapy Oncology Group (RTOG) cosmetic rating scale, in patients treated with this regimen compared with that of patients treated with partial breast brachytherapy in clinical trial RTOG-9517. Determine the incidence of grade 3-4 toxicity of this regimen in these patients. Determine the rate of ipsilateral breast recurrence, including recurrence within the tumor bed as compared to elsewhere in the breast, in patients treated with this regimen. Secondary Determine the radiation-induced activation of receptors and signal transduction pathways involved in radiation response in patients treated with this regimen. OUTLINE: This is a non-randomized study. Patients undergo intraoperative lymphatic mapping and sentinel lymphadenectomy OR standard level I, II axillary dissection to evaluate the lymph nodes followed by intraoperative breast ultrasonography to define the tumor target volume. Patients then undergo intraoperative single-dose partial breast radiotherapy followed by segmental mastectomy (i.e., lumpectomy) of the tumor. Patients with 1 or 2 tumor-involved surgical margins may undergo repeat segmental mastectomy. Patients with > 2 tumor-involved surgical margins undergo mastectomy. Patients determined to have a tumor size > 3 cm or an extensive intraductal component on final pathology evaluation undergo standard external beam radiotherapy after surgery. After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study within 2 to 3 years.

Official Title
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Partial Breast Treatment Using Single Dose Intraoperative Radiotherapy for Patients With Early Stage Breast Cancer - A Feasibility Study With Molecular Analysis of Tumors and Normal Breast Epithelial Tissue

Conditions
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Breast Cancer

Intervention / Treatment
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* Procedure: surgery
* Procedure: therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed primary invasive ductal carcinoma of the breast Tumor size ≤ 3 cm No extensive intraductal component Tumor must not be attached to the skin, underlying muscle, or chest wall Candidate for breast-conserving therapy, as determined by the surgical and radiation oncologist Tumor amenable to segmental mastectomy (i.e., lumpectomy) No bilateral breast cancer No clinical or radiographic multifocal disease not amenable to single segmental mastectomy Patients with > 1 tumor mass in the same breast must have only 1 mass that is histologically malignant AND all other masses must be proven histologically benign Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 48 and over Sex Female Menopausal status Not specified Performance status 0-2 Life expectancy At least 5 years Hematopoietic Not specified Hepatic Not specified Renal Not specified Other Not pregnant Fertile patients must use effective contraception No collagen vascular disease No medical condition that would preclude surgery Other prior malignancy allowed provided the following criteria are met: Patient has undergone potential curative therapy for all prior malignancies There is no evidence of any prior malignancy within the past 5 years Patient is deemed to be at low risk for recurrence of prior malignancy, as determined by the treating physician PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy for this malignancy Endocrine therapy Not specified Radiotherapy No prior radiotherapy to the breast Surgery No breast implants

Ages Eligible for Study
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Minimum Age: 48 Years
Maximum Age: 120 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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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intraoperative Radiation Arm<br>Intraoperative radiotherapy (radiation therapy) during surgery for tumor excision. | Procedure: surgery<br>* conventional<br>Procedure: therapy<br>* neoadjuvant<br>Radiation: radiation therapy<br>* intraoperative radiation therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of Good/Excellent Cosmesis as Measured by the Radiation Therapy Oncology Group (RTOG) Cosmetic Rating Scale - Rated by Physician | Rates of good/excellent cosmesis was evaluated using the following criteria: Excellent - when compared to the untreated breast, there is minimal or no difference in the size, shape, or texture of the treated breast. There may be mild thickening or scar tissue within the breast or skin, but not enough to change the appearance. Good - there is mild asymmetry in the size or shape of the treated breast as compared to the normal breast. The thickening or scar tissue within the breast causes only a mild change in the shape. | 1 year follow up visit | 
| Rates of Good/Excellent Cosmesis as Measured by the Radiation Therapy Oncology Group (RTOG) Cosmetic Rating Scale - Rated by Patients | Rates of good/excellent cosmesis was evaluated using the following criteria: Excellent - when compared to the untreated breast, there is minimal or no difference in the size, shape, or texture of the treated breast. There may be mild thickening or scar tissue within the breast or skin, but not enough to change the appearance. Good - there is mild asymmetry in the size or shape of the treated breast as compared to the normal breast. The thickening or scar tissue within the breast causes only a mild change in the shape. | 1 year follow up visit | 
| Incidence of Grade 3/4 Toxicity | Skin and subcutaneous toxicity were graded by a radiation oncologist according to the common terminology criteria for adverse events version 3.0. Toxicities directly, probably, or possibly related to the radiation were included. Grade refers to the severity of the AE. The CTCAE v3.0 displays Grades 1 through 5 with unique clinical descriptions of severity for each adverse event (AE) based on this general guideline: Grade 1 Mild Adverse Event Grade 2 Moderate Adverse Event Grade 3 Severe Adverse Event Grade 4 Life-threatening or disabling Adverse Event Grade 5 Death related to Adverse Event | 3 months | 
| Ipsilateral Breast Recurrence | Percentage of participants who experienced a ipsilateral breast event (tumor bed recurrence versus elsewhere in breast). | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association of Phosphorylated Epidermal Growth Factor Receptor (EGFR) , Human Epidermal Growth Factor Receptor 2 (HER2), p44/42 Mitogen-activated Protein Kinase (MAPK), and Protein Kinase B (Akt) in Breast Tumors and Normal Tissue Before and After IORT |  | 3 months | 
| Association of Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells (NFkB) Expression in Tumor and Normal Tissue Before and After IORT |  | 3 months | 
| Association of Nuclear p53 Expression in Tumor and Normal Tissue Before and After IORT |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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invasive ductal breast carcinoma, stage I breast cancer, stage II breast cancer