Breast Cancer
Conditions
Brief summary
Over the past two decades, breast conserving therapy (BCT) has become a major treatment modality for Stage I and II breast carcinoma. The major advantages of breast conserving therapy are superior cosmetic outcome and the reduced emotional and psychological trauma afforded by this procedure compared with conventional mastectomy. The principal disadvantage of BCT is its more complex and prolonged treatment regimen requiring approximately 6 weeks of external beam radiation therapy that poses problems for some patients such as the working woman, elderly patients, and those who live at a significant distance from a treatment center. These factors, along with the patient's geographic location, result in a smaller fraction of the patients who currently meet eligibility criteria for BCT actually receiving it, despite its cosmetic and probable psychological advantages. The logistical problems of BCT are primarily related to the protracted course of external beam radiation therapy to the whole breast. While some investigators reported what they believe to be acceptable local control rates in carefully selected patients treated by wide local excision without radiation therapy, the criteria for patient selection are controversial and poorly defined and probably restrict the access of many patients to breast conserving therapy. If previous observations are valid and breast irradiation following tylectomy exerts its maximal effect in eradicating occult disease remaining in the immediate vicinity of the tylectomy site, can radiation therapy be directed only to the tissue surrounding the excision cavity of the breast, using brachytherapy alone? If so, the entire course of radiation therapy could be delivered over a 4 to 7 day period immediately following tylectomy and/or axillary dissection, thus markedly reducing treatment time. Brachytherapy also inherently provides a higher central dose to the volume most at risk for recurrence. Cosmetic outcome after the use of a brachytherapy boost after external whole breast radiotherapy is comparable or slightly inferior to electron beam boost radiation therapy
Detailed description
This study will evaluate the local control, cosmetic results, quality of life, and complication rates of brachytherapy when used as the sole method of radiation therapy for patients with stage 0,I, and II carcinoma of the breast treated with tylectomy, with histologically assessed negative surgical margins, N0 axillary nodes.
Interventions
RADIATIONbrachytherapy
brachytherapy (radioactive implants)
Sponsors
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* AJCC stage 0, I, or II (TisN0, T1N0, T2N0 = 3 cm) histologically confirmed carcinoma of the breast, treated with tylectomy. Axillary sampling is required only for cases of invasive cancers. Tumor size is determined by the pathologist. Clinical size may be used if the pathologic size is indeterminate. * Signed study-specific informed consent for participation in the study. * Negative, or close but negative, inked histologic margins of tylectomy or reexcision specimen to be confirmed prior to placing the brachytherapy catheters. Margins generally are positive if there is invasive or noninvasive tumor at the inked resection margin, close but negative if the tumor is within 2 mm of the inked margin and negative if the tumor is at least 2 mm away from the inked edge. * Negative post-tylectomy or post-reexcision mammography if cancer presented with malignancy-associated microcalcifications; no remaining suspicious microcalcifications in the breast before brachytherapy. * For patients with invasive cancer, no positive axillary lymph nodes with at least 6 axillary lymph nodes sampled or a negative sentinel node. * Invasive ductal, lobular, medullary, papillary, colloid (mucinous),or tubular histologies. Noninvasive ductal carcinoma in situ. * Chemotherapy or hormonal therapy planned for = 2 weeks after removal of brachytherapy catheters is permitted. Hormonal therapy is allowed during brachytherapy at treating radiation oncologist's decision. * Negative pregnancy test for premenopausal patients with an intact uterus
Exclusion criteria
* Patients with distant metastases. * Patients with in-situ lobular carcinoma or nonepithelial breast malignancies such as sarcoma or lymphoma. * Patients with proven multicentric carcinoma (tumors in different quadrants of the breast, or tumors separated by at least 4 cm) with other clinically or radiographically suspicious areas in the ipsilateral breast unless confirmed to be negative for malignancy by biopsy. * Patients who are pregnant or lactating. * Patients with histologically confirmed positive axillary nodes in the ipsilateral axilla. Palpable or radiographically suspicious contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes, unless there is histologic confirmation that these nodes are negative for tumor. * Prior non-hormonal therapy for the present breast cancer, including radiation therapy or chemotherapy. * Patients with systemic lupus erythematosis, scleroderma, or dermatomyositis with a CPK level above normal or with an active skin rash. * Patients with coexisting medical conditions in whom life expectancy is \< 2 years. * Patients with psychiatric or addictive disorders that would preclude obtaining informed consent or completing the full series of high dose rate brachytherapy treatments on an outpatient basis. * Patients with Paget's disease of the nipple. * Patients with skin involvement, regardless of tumor size. * Patients with a breast unsatisfactory for brachytherapy. For example, if there is little breast tissue remaining between the skin and pectoralis muscle after surgery, placement of catheters is technically problematic. * Patients with tylectomies so extensive that the cosmetic result is fair or poor prior to brachytherapy. * Surgical margins which cannot be microscopically assessed or are positive at pathological evaluation. * Any previously treated contralateral breast carcinoma or synchronous bilateral breast carcinoma. * Other malignancy, except non-melanoma skin cancer, ≤ 5 years prior to participation in this study; the disease free interval from any prior carcinoma must be continuous. * Time between final definitive breast procedure to radioactive source loading of the brachytherapy catheters is greater than 8 weeks. * Patients with diffuse (\> 1 quadrant or \>5 cm in diameter) suspicious microcalcifications. * Patients with suspicious microcalcifications remaining on the post-tylectomy mammogram
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Local Control Using Ipsilateral Breast Tumor Recurrence Rates | 2 years after treatment completion |
| Local Control as Measured by Ipsilateral Breast Tumor Recurrence Rates | 5 years after treatment completion |
| Local Control Using Disease-free Survival Rates | 2 years after treatment completion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Impressions of the Cause of Cosmesis Changes Over Time - Patient Reported | 3 years | -Patients filled out a form Patient Evaluation of the Treated Breast. On this form the patients were asked to compare the memory of what their breast looked like after surgery but before radiation and to compare that memory to the appearance of the breast after radiation. The patients were then asked if their breast changes were due to: * caused mostly by radiation * caused by both the radiation and surgery, but mostly by the radiation * caused by both the radiation and surgery, but mostly by the surgery * caused mostly by the surgery * can't judge which treatment caused the change * there are no changes |
| Cosmesis Outcome as Measured by Percentage of Breast Retraction Assessment (pBRA) | Pre-treatment and 3 years | -Cosmetic outcome was evaluated quantitatively by percentage of breast retraction assessment (pBRA) |
| Quality of Life Completion | 2 years | -QOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC breast cancer module QLQ-BR23 questionnaires. QLQ-C30 is composed of 30 questions. QLQ-BR23 consists of 23 questions. |
| Occurrence of Mastectomy After Completion of Initial Breast-conserving Treatment | 5 years after treatment completion | — |
| Frequency of Grade 3-4 Toxicities | Up to 1 year from completion of therapy | RTOG acute and late toxicity grading system and via a visual analog scale for pain assessment. |
| Presence or Absence of Complications | 5 years after treatment completion | As defined by number of participants who experienced breast infection and symptomatic fat necrosis. |
| Excellent-good Cosmetic Outcomes - Patient Reported | 3 years after completion of therapy | * Both the participants and the treating radiation oncologist qualitatively rated cosmesis as excellent, good, fair, or poor over time and ascribed a cause for changes in cosmesis. * The global cosmetic result were scored on a 4-point scare where 0=excellent result (no difference), 1=good (small difference), 2=fair result (moderate difference) and 3=poor result (large difference). |
| Excellent-good Cosmetic Outcomes - Physician Reported | 3 years after completion of therapy | * Both the participants and the treating radiation oncologist qualitatively rated cosmesis as excellent, good, fair, or poor over time and ascribed a cause for changes in cosmesis. Cosmetic outcome was evaluated quantitatively by percentage of breast retraction assessment (pBRA). * The global cosmetic result were scored on a 4-point scale where 0=excellent result (no difference), 1=good (small difference), 2=fair result (moderate difference) and 3=poor result (large difference). |
Countries
United States
Participant flow
Recruitment details
The study opened to participant enrollment on March 12, 2004 and closed to participant enrollment on 12/22/2008.
Participants by arm
| Arm | Count |
|---|---|
| Accelerated Partial Breast Brachytherapy Each patient will receive accelerated partial breast brachytherapy with multiple plane implant.
Patients will receive 3400 cGy delivered in 10 twice-daily fractions. Treatment is to be given over 5-7 days with a minimum of 6 hours separation between fractions. | 151 |
| Total | 151 |
Baseline characteristics
| Characteristic | Accelerated Partial Breast Brachytherapy |
|---|---|
| Age, Continuous | 60 years |
| Pathologic tumor stage T1a | 19 participants |
| Pathologic tumor stage T1b | 52 participants |
| Pathologic tumor stage T1c | 38 participants |
| Pathologic tumor stage T1mic | 1 participants |
| Pathologic tumor stage T2 | 13 participants |
| Pathologic tumor stage Tis | 28 participants |
| Race African-American | 23 participants |
| Race Caucasian | 128 participants |
| Region of Enrollment United States | 151 participants |
| Residence at diagnosis Rural | 15 participants |
| Residence at diagnosis Urban area | 111 participants |
| Residence at diagnosis Urban cluster | 25 participants |
| Sentinel lymph node biopsy No | 1 participants |
| Sentinel lymph node biopsy Yes | 122 participants |
| Sex: Female, Male Female | 151 Participants |
| Sex: Female, Male Male | 0 Participants |
| Tumor location Lower inner quadrant | 21 participants |
| Tumor location Lower outer quadrant | 30 participants |
| Tumor location Upper inner quadrant | 46 participants |
| Tumor location Upper outer quadrant | 54 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 151 / 151 |
| serious Total, serious adverse events | 0 / 151 |
Outcome results
Primary
Local Control as Measured by Ipsilateral Breast Tumor Recurrence Rates
Time frame: 5 years after treatment completion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Accelerated Partial Breast Brachytherapy | Local Control as Measured by Ipsilateral Breast Tumor Recurrence Rates | 3.4 percentage of participants |
Primary
Local Control Using Disease-free Survival Rates
Time frame: 5 years after treatment completion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Accelerated Partial Breast Brachytherapy | Local Control Using Disease-free Survival Rates | 94.4 percentage of participants |
Primary
Local Control Using Disease-free Survival Rates
Time frame: 2 years after treatment completion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Accelerated Partial Breast Brachytherapy | Local Control Using Disease-free Survival Rates | 99.3 percentage of participants |
Primary
Local Control Using Ipsilateral Breast Tumor Recurrence Rates
Time frame: 2 years after treatment completion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Accelerated Partial Breast Brachytherapy | Local Control Using Ipsilateral Breast Tumor Recurrence Rates | .7 percentage of participants |
Secondary
Cosmesis Outcome as Measured by Percentage of Breast Retraction Assessment (pBRA)
-Cosmetic outcome was evaluated quantitatively by percentage of breast retraction assessment (pBRA)
Time frame: Pre-treatment and 3 years
Population: 82 participants had cosmetic outcome data through 3 years of follow-up.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Accelerated Partial Breast Brachytherapy | Cosmesis Outcome as Measured by Percentage of Breast Retraction Assessment (pBRA) | Pre-treatment | 7.35 percentage of breast retraction |
| Accelerated Partial Breast Brachytherapy | Cosmesis Outcome as Measured by Percentage of Breast Retraction Assessment (pBRA) | 3 years | 7.64 percentage of breast retraction |
Secondary
Excellent-good Cosmetic Outcomes - Patient Reported
* Both the participants and the treating radiation oncologist qualitatively rated cosmesis as excellent, good, fair, or poor over time and ascribed a cause for changes in cosmesis. * The global cosmetic result were scored on a 4-point scare where 0=excellent result (no difference), 1=good (small difference), 2=fair result (moderate difference) and 3=poor result (large difference).
Time frame: 3 years after completion of therapy
Population: 82 participants had cosmetic outcome data through 3 years of follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Accelerated Partial Breast Brachytherapy | Excellent-good Cosmetic Outcomes - Patient Reported | Pre-treatment | 92 percentage of participants |
| Accelerated Partial Breast Brachytherapy | Excellent-good Cosmetic Outcomes - Patient Reported | 3-4 months after treatment | 91 percentage of participants |
| Accelerated Partial Breast Brachytherapy | Excellent-good Cosmetic Outcomes - Patient Reported | 2 years | 87 percentage of participants |
| Accelerated Partial Breast Brachytherapy | Excellent-good Cosmetic Outcomes - Patient Reported | 3 years | 92 percentage of participants |
Secondary
Excellent-good Cosmetic Outcomes - Physician Reported
* Both the participants and the treating radiation oncologist qualitatively rated cosmesis as excellent, good, fair, or poor over time and ascribed a cause for changes in cosmesis. Cosmetic outcome was evaluated quantitatively by percentage of breast retraction assessment (pBRA). * The global cosmetic result were scored on a 4-point scale where 0=excellent result (no difference), 1=good (small difference), 2=fair result (moderate difference) and 3=poor result (large difference).
Time frame: 3 years after completion of therapy
Population: 82 participants had cosmetic outcome data through 3 years of follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Accelerated Partial Breast Brachytherapy | Excellent-good Cosmetic Outcomes - Physician Reported | Pre-treatment | 97 percentage of participants |
| Accelerated Partial Breast Brachytherapy | Excellent-good Cosmetic Outcomes - Physician Reported | 3-4 months after treatment | 97 percentage of participants |
| Accelerated Partial Breast Brachytherapy | Excellent-good Cosmetic Outcomes - Physician Reported | 2 years | 94 percentage of participants |
| Accelerated Partial Breast Brachytherapy | Excellent-good Cosmetic Outcomes - Physician Reported | 3 years | 94 percentage of participants |
Secondary
Frequency of Grade 3-4 Toxicities
RTOG acute and late toxicity grading system and via a visual analog scale for pain assessment.
Time frame: Up to 1 year from completion of therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Accelerated Partial Breast Brachytherapy | Frequency of Grade 3-4 Toxicities | Late pulmonary - Grade 3/4 | 0 participants |
| Accelerated Partial Breast Brachytherapy | Frequency of Grade 3-4 Toxicities | Acute skin - Grade 3/4 | 1 participants |
| Accelerated Partial Breast Brachytherapy | Frequency of Grade 3-4 Toxicities | Acute breast infection - Grade 3/4 | 2 participants |
| Accelerated Partial Breast Brachytherapy | Frequency of Grade 3-4 Toxicities | Acute subcutaneous - Grade 3/4 | 0 participants |
| Accelerated Partial Breast Brachytherapy | Frequency of Grade 3-4 Toxicities | Late skin - Grade 3/4 | 0 participants |
| Accelerated Partial Breast Brachytherapy | Frequency of Grade 3-4 Toxicities | Late subcutaneous | 0 participants |
| Accelerated Partial Breast Brachytherapy | Frequency of Grade 3-4 Toxicities | Late heart - Grade 3/4 | 0 participants |
Secondary
Impressions of the Cause of Cosmesis Changes Over Time - Patient Reported
-Patients filled out a form Patient Evaluation of the Treated Breast. On this form the patients were asked to compare the memory of what their breast looked like after surgery but before radiation and to compare that memory to the appearance of the breast after radiation. The patients were then asked if their breast changes were due to: * caused mostly by radiation * caused by both the radiation and surgery, but mostly by the radiation * caused by both the radiation and surgery, but mostly by the surgery * caused mostly by the surgery * can't judge which treatment caused the change * there are no changes
Time frame: 3 years
Population: 82 participants had cosmetic outcome data through 3 years of follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Accelerated Partial Breast Brachytherapy | Impressions of the Cause of Cosmesis Changes Over Time - Patient Reported | Radiation | 16.5 percentage of participants |
| Accelerated Partial Breast Brachytherapy | Impressions of the Cause of Cosmesis Changes Over Time - Patient Reported | Surgery | 57 percentage of participants |
| Accelerated Partial Breast Brachytherapy | Impressions of the Cause of Cosmesis Changes Over Time - Patient Reported | Unsure | 19 percentage of participants |
| Accelerated Partial Breast Brachytherapy | Impressions of the Cause of Cosmesis Changes Over Time - Patient Reported | No cosmetic changes | 7.5 percentage of participants |
Secondary
Occurrence of Mastectomy After Completion of Initial Breast-conserving Treatment
Time frame: 5 years after treatment completion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Accelerated Partial Breast Brachytherapy | Occurrence of Mastectomy After Completion of Initial Breast-conserving Treatment | 4 participants |
Secondary
Presence or Absence of Complications
As defined by number of participants who experienced breast infection and symptomatic fat necrosis.
Time frame: 5 years after treatment completion
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Accelerated Partial Breast Brachytherapy | Presence or Absence of Complications | Breast infection | 6 participants |
| Accelerated Partial Breast Brachytherapy | Presence or Absence of Complications | Fat necrosis (symptomatic) | 19 participants |
Secondary
Quality of Life Completion
-QOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC breast cancer module QLQ-BR23 questionnaires. QLQ-C30 is composed of 30 questions. QLQ-BR23 consists of 23 questions.
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Accelerated Partial Breast Brachytherapy | Quality of Life Completion | 6-8 weeks | 99 percentage of participants |
| Accelerated Partial Breast Brachytherapy | Quality of Life Completion | 3-4 months | 95 percentage of participants |
| Accelerated Partial Breast Brachytherapy | Quality of Life Completion | 6-8 months | 91 percentage of participants |
| Accelerated Partial Breast Brachytherapy | Quality of Life Completion | 1 year | 88 percentage of participants |
| Accelerated Partial Breast Brachytherapy | Quality of Life Completion | 2 years | 74 percentage of participants |