Breast Cancer
Conditions
Keywords
invasive ductal breast carcinoma, stage I breast cancer, stage II breast cancer
Brief summary
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
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.
Interventions
PROCEDUREsurgery
conventional
PROCEDUREtherapy
neoadjuvant
RADIATIONradiation therapy
intraoperative radiation therapy
Sponsors
UNC Lineberger Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
48 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rates of Good/Excellent Cosmesis as Measured by the Radiation Therapy Oncology Group (RTOG) Cosmetic Rating Scale - Rated by Physician | 1 year follow up visit | 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. |
| Rates of Good/Excellent Cosmesis as Measured by the Radiation Therapy Oncology Group (RTOG) Cosmetic Rating Scale - Rated by Patients | 1 year follow up visit | 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. |
| Incidence of Grade 3/4 Toxicity | 3 months | 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 |
| Ipsilateral Breast Recurrence | 5 years | Percentage of participants who experienced a ipsilateral breast event (tumor bed recurrence versus elsewhere in breast). |
Secondary
| Measure | 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 |
Countries
United States
Participant flow
Recruitment details
March 2003 to July 2007
Pre-assignment details
89 patients consented. Of those 89, 18 were not treated for the following reasons: tumor not seen on ultrasound (2), tumor too close to chest wall (7), tumor too large (1), ineligible pathology (1), ineligible nodal status (1), operating room logistical errors (3), patients withdrew (2), not eligible for anesthesia (1).
Participants by arm
| Arm | Count |
|---|---|
| Intraoperative Radiation Arm Intraoperative radiotherapy (radiation therapy) during surgery for tumor excision.
surgery: conventional
therapy: neoadjuvant
radiation therapy: intraoperative radiation therapy | 71 |
| Total | 71 |
Baseline characteristics
| Characteristic | Intraoperative Radiation Arm |
|---|---|
| Age, Continuous | 64.8 years |
| Clinical Staging cN0 | 71 Participants |
| Clinical Staging cT1a | 2 Participants |
| Clinical Staging cT1b | 18 Participants |
| Clinical Staging cT1c | 35 Participants |
| Clinical Staging cT2 (<3 cm) | 16 Participants |
| Grade I | 25 Participants |
| Grade II | 24 Participants |
| Grade III | 22 Participants |
| Markers ER+, PR+, HER2- | 46 Participants |
| Markers Estrogen Receptor (ER) positive | 54 Participants |
| Markers Human Epidermal Growth Factor receptor (HER) 2 pos | 8 Participants |
| Markers Progesterone Receptor (PR) positive | 50 Participants |
| Markers triple negative | 12 Participants |
| Region of Enrollment United States | 71 Participants |
| Sex: Female, Male Female | 71 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 71 |
| other Total, other adverse events | 11 / 71 |
| serious Total, serious adverse events | 0 / 71 |
Outcome results
Primary
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
Time frame: 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intraoperative Radiation Arm | Incidence of Grade 3/4 Toxicity | 0 Participants |
Primary
Ipsilateral Breast Recurrence
Percentage of participants who experienced a ipsilateral breast event (tumor bed recurrence versus elsewhere in breast).
Time frame: 5 years
Population: There were 71 patients who received IORT. Of those 71 patients, 18 received further local therapy due to high risk pathology. The results include the 53 patients who received IORT without further local therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intraoperative Radiation Arm | Ipsilateral Breast Recurrence | 13 percentage of participants |
Primary
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.
Time frame: 1 year follow up visit
Population: Patients who received IORT alone. 42 patients assessed their cosmetic outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intraoperative Radiation Arm | Rates of Good/Excellent Cosmesis as Measured by the Radiation Therapy Oncology Group (RTOG) Cosmetic Rating Scale - Rated by Patients | 32 Participants |
Primary
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.
Time frame: 1 year follow up visit
Population: Patients who received intraoperative radiation therapy (IORT) alone. 56 patients were assessed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intraoperative Radiation Arm | Rates of Good/Excellent Cosmesis as Measured by the Radiation Therapy Oncology Group (RTOG) Cosmetic Rating Scale - Rated by Physician | 45 Participants |
Secondary
Association of Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells (NFkB) Expression in Tumor and Normal Tissue Before and After IORT
Time frame: 3 months
Population: No data were collected for this biomarker. Although samples were obtained from patients, they were never processed and analyzed.
Secondary
Association of Nuclear p53 Expression in Tumor and Normal Tissue Before and After IORT
Time frame: 3 months
Population: No data were collected for this biomarker. Although samples were obtained from patients, they were never processed and analyzed.
Secondary
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
Time frame: 3 months
Population: No data were collected for any of these biomarkers. Although samples were obtained from patients, they were never processed and analyzed.