Brief Summary
The purpose of this study is to test whether patients undergoing a breast MRI (magnetic resonance imaging) before breast surgery will have better results after the surgery. Breast tumors are routinely evaluated using mammograms and ultrasound before surgery. This study would like to find out if using MRI in addition to mammography before surgery improves our ability to evaluate tumors and decide what kind of surgery is best for the patient.
Brief Title
MRI and Mammography Before Surgery in Patients With Stage I-II Breast Cancer
Detailed Description
This is a randomized trial of preoperative breast MRI in patients deemed eligible for breast conserving surgery by conventional clinical criteria will provide important information about the clinical and biologic relevance of occult disease identified by MRI alone. Patients will be assigned to standard pre-operative breast cancer disease assessment without the addition of MRI prior to breast conserving surgery or standard pre-operative breast cancer disease assessment with the use of MRI prior to breast conserving surgery.
The primary objective is to compare the rates of local-regional recurrence (LRR) following attempted breast conserving therapy in a cohort of women with triple negative or HER-2 amplified breast cancer randomized to preoperative staging with mammography (control arm) or mammography plus breast MRI (MRI arm).
Secondary objectives are:
* To compare the re-operation rates following attempted breast conserving therapy between women assessed preoperatively with breast MRI to those assessed without the use of breast MRI
* To compare local recurrence rates between women who undergo BCT on the control arm to women who undergo BCT on the MRI arm
* To compare the conversion rate to mastectomy secondary to persistent positive margins or poor cosmesis within the first 6 months of attempting BCT (prior to the administration of RT) between women assessed preoperatively with breast MRI to those assessed without the use of breast MRI
* To compare the contralateral breast cancer rates in women randomized to preoperative breast MRI to those not receiving pre-operative breast MRI
* To compare the disease-free survival rates between women assessed preoperatively with breast MRI to those assessed without the use of breast MRI
* To compare breast cancer specific and overall survival outcomes of women assessed preoperatively with breast MRI to those assessed without the use of breast MRI
* To estimate the rate of MRI-guided localization assisted surgery
* To estimate the rate of multi-centric disease in the index breast for women in the MRI arm
* To evaluate the accuracy of index lesion characteristics and other factors in predicting multi-centricity in the cohort randomized to breast MRI
* To assess the positive predictive values (PPV) of MRI in detecting ipsilateral multi-centric disease and contralateral disease in women with breast cancer undergoing preoperative breast MRI
* To estimate the false positive rate for detection of multiple foci of breast cancer by MRI
All registered patients will be monitored for relapse and survival for 5 years from the date of surgery. Patients will be followed a minimum of every 4 months for the first 2 years from diagnosis and a minimum of every 6 months during years 3-5. Patients will be monitored for local, regional, distant relapse and vital status.
The primary objective is to compare the rates of local-regional recurrence (LRR) following attempted breast conserving therapy in a cohort of women with triple negative or HER-2 amplified breast cancer randomized to preoperative staging with mammography (control arm) or mammography plus breast MRI (MRI arm).
Secondary objectives are:
* To compare the re-operation rates following attempted breast conserving therapy between women assessed preoperatively with breast MRI to those assessed without the use of breast MRI
* To compare local recurrence rates between women who undergo BCT on the control arm to women who undergo BCT on the MRI arm
* To compare the conversion rate to mastectomy secondary to persistent positive margins or poor cosmesis within the first 6 months of attempting BCT (prior to the administration of RT) between women assessed preoperatively with breast MRI to those assessed without the use of breast MRI
* To compare the contralateral breast cancer rates in women randomized to preoperative breast MRI to those not receiving pre-operative breast MRI
* To compare the disease-free survival rates between women assessed preoperatively with breast MRI to those assessed without the use of breast MRI
* To compare breast cancer specific and overall survival outcomes of women assessed preoperatively with breast MRI to those assessed without the use of breast MRI
* To estimate the rate of MRI-guided localization assisted surgery
* To estimate the rate of multi-centric disease in the index breast for women in the MRI arm
* To evaluate the accuracy of index lesion characteristics and other factors in predicting multi-centricity in the cohort randomized to breast MRI
* To assess the positive predictive values (PPV) of MRI in detecting ipsilateral multi-centric disease and contralateral disease in women with breast cancer undergoing preoperative breast MRI
* To estimate the false positive rate for detection of multiple foci of breast cancer by MRI
All registered patients will be monitored for relapse and survival for 5 years from the date of surgery. Patients will be followed a minimum of every 4 months for the first 2 years from diagnosis and a minimum of every 6 months during years 3-5. Patients will be monitored for local, regional, distant relapse and vital status.
Conditions
Estrogen Receptor-negative Breast Cancer
Progesterone Receptor-negative Breast Cancer
Stage IA Breast Cancer
Stage IB Breast Cancer
Stage II Breast Cancer
Triple-negative Breast Cancer
Eligibility Criteria
* Female. Men are excluded from this study because the number of men with breast cancer is insufficient to provide a statistical basis for assessment of effects in this subpopulation of people with breast cancer.
* Pathologically confirmed diagnosis of breast cancer, clinical stage I-II (T1-3 N0 M0, T0-2 N1 M0). Diagnosis must be by needle biopsy; patients diagnosed by surgical excision are excluded.
* Patients must have either:
* Estrogen receptor (ER) negative/progesterone receptor (PR) negative (\< 10% by immunohistochemistry IHC staining) and HER-2 negative breast cancer OR
* ER negative/PR negative (\< 10% by IHC staining) and HER-2 positive tumors
* HER-2 status will be determined as per the 2013 ASCO CAP guidelines:
* HER-2 is considered positive if there is IHC 3+ staining or ISH positive using either single probe ISH or dual probe ISH
* HER-2 is considered negative if there is IHC 0 or 1+ staining or ISH negative using either single probe ISH or dual probe ISH
* No patients with previous ipsilateral invasive breast cancer or ductal carcinoma in situ (DCIS)
* No patients with bilateral breast cancer
* No patients with known deleterious mutations in breast cancer (BRCA) genes
* No current history of receiving hormonal therapy, tamoxifen, and or aromatase inhibitors for therapeutic measures
* No history of chemotherapy for cancer within 6 months prior to registration
* No patients scheduled to receive neoadjuvant chemotherapy or partial breast irradiation following breast conserving surgery
* Eligible for BCT based on clinical examination, mammography and, if standard practice at a given institution, ultrasound and/or tomogram. Women who cannot be appropriately selected for BCT based on these standard imaging studies, and for whom additional imaging is recommended to clarify local disease extent, will not be eligible for this trial.
* No patients with multicentric or multifocal disease scheduled to undergo multiple lumpectomies. Multifocal disease that can be encompassed in a single operative bed can be enrolled.
* Suitable to undergo MRI and receive the contrast agent gadolinium (exclusions follow):
* No history of untreatable claustrophobia
* No presence of metallic objects or implanted medical devices in body (i.e., cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants)
* No history of sickle cell disease
* No contraindication to intravenous contrast administration
* No known allergy-like reaction to gadolinium or moderate or severe allergic reactions to one or more allergens as defined by the American College of Radiology (ACR); patient may be eligible if willing to undergo pre-treatment as defined by the institution's policy and/or ACR guidance
* No findings consistent with renal failure, as determined by glomerular filtration rate (GFR) \< 30 mL/min/1.73 m\^2 based on a creatinine level obtained within 28 days prior to registration
* Weight lower than that allowable by the MRI table
* No prior MRI of study breast within the 12 months prior to registration
* Non-pregnant and non-lactating. Patients of child-bearing potential must have a negative pregnancy test within 7 days prior to registration. Perimenopausal patients must be amenorrheic \> 12 months to be considered not of child-bearing potential
* ≥ 18 years of age
* Signed study-specific informed consent prior to registration
* Pathologically confirmed diagnosis of breast cancer, clinical stage I-II (T1-3 N0 M0, T0-2 N1 M0). Diagnosis must be by needle biopsy; patients diagnosed by surgical excision are excluded.
* Patients must have either:
* Estrogen receptor (ER) negative/progesterone receptor (PR) negative (\< 10% by immunohistochemistry IHC staining) and HER-2 negative breast cancer OR
* ER negative/PR negative (\< 10% by IHC staining) and HER-2 positive tumors
* HER-2 status will be determined as per the 2013 ASCO CAP guidelines:
* HER-2 is considered positive if there is IHC 3+ staining or ISH positive using either single probe ISH or dual probe ISH
* HER-2 is considered negative if there is IHC 0 or 1+ staining or ISH negative using either single probe ISH or dual probe ISH
* No patients with previous ipsilateral invasive breast cancer or ductal carcinoma in situ (DCIS)
* No patients with bilateral breast cancer
* No patients with known deleterious mutations in breast cancer (BRCA) genes
* No current history of receiving hormonal therapy, tamoxifen, and or aromatase inhibitors for therapeutic measures
* No history of chemotherapy for cancer within 6 months prior to registration
* No patients scheduled to receive neoadjuvant chemotherapy or partial breast irradiation following breast conserving surgery
* Eligible for BCT based on clinical examination, mammography and, if standard practice at a given institution, ultrasound and/or tomogram. Women who cannot be appropriately selected for BCT based on these standard imaging studies, and for whom additional imaging is recommended to clarify local disease extent, will not be eligible for this trial.
* No patients with multicentric or multifocal disease scheduled to undergo multiple lumpectomies. Multifocal disease that can be encompassed in a single operative bed can be enrolled.
* Suitable to undergo MRI and receive the contrast agent gadolinium (exclusions follow):
* No history of untreatable claustrophobia
* No presence of metallic objects or implanted medical devices in body (i.e., cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants)
* No history of sickle cell disease
* No contraindication to intravenous contrast administration
* No known allergy-like reaction to gadolinium or moderate or severe allergic reactions to one or more allergens as defined by the American College of Radiology (ACR); patient may be eligible if willing to undergo pre-treatment as defined by the institution's policy and/or ACR guidance
* No findings consistent with renal failure, as determined by glomerular filtration rate (GFR) \< 30 mL/min/1.73 m\^2 based on a creatinine level obtained within 28 days prior to registration
* Weight lower than that allowable by the MRI table
* No prior MRI of study breast within the 12 months prior to registration
* Non-pregnant and non-lactating. Patients of child-bearing potential must have a negative pregnancy test within 7 days prior to registration. Perimenopausal patients must be amenorrheic \> 12 months to be considered not of child-bearing potential
* ≥ 18 years of age
* Signed study-specific informed consent prior to registration
Inclusion Criteria
* Female. Men are excluded from this study because the number of men with breast cancer is insufficient to provide a statistical basis for assessment of effects in this subpopulation of people with breast cancer.
* Pathologically confirmed diagnosis of breast cancer, clinical stage I-II (T1-3 N0 M0, T0-2 N1 M0). Diagnosis must be by needle biopsy; patients diagnosed by surgical excision are excluded.
* Patients must have either:
* Estrogen receptor (ER) negative/progesterone receptor (PR) negative (\< 10% by immunohistochemistry IHC staining) and HER-2 negative breast cancer OR
* ER negative/PR negative (\< 10% by IHC staining) and HER-2 positive tumors
* HER-2 status will be determined as per the 2013 ASCO CAP guidelines:
* HER-2 is considered positive if there is IHC 3+ staining or ISH positive using either single probe ISH or dual probe ISH
* HER-2 is considered negative if there is IHC 0 or 1+ staining or ISH negative using either single probe ISH or dual probe ISH
* No patients with previous ipsilateral invasive breast cancer or ductal carcinoma in situ (DCIS)
* No patients with bilateral breast cancer
* No patients with known deleterious mutations in breast cancer (BRCA) genes
* No current history of receiving hormonal therapy, tamoxifen, and or aromatase inhibitors for therapeutic measures
* No history of chemotherapy for cancer within 6 months prior to registration
* No patients scheduled to receive neoadjuvant chemotherapy or partial breast irradiation following breast conserving surgery
* Eligible for BCT based on clinical examination, mammography and, if standard practice at a given institution, ultrasound and/or tomogram. Women who cannot be appropriately selected for BCT based on these standard imaging studies, and for whom additional imaging is recommended to clarify local disease extent, will not be eligible for this trial.
* No patients with multicentric or multifocal disease scheduled to undergo multiple lumpectomies. Multifocal disease that can be encompassed in a single operative bed can be enrolled.
* Suitable to undergo MRI and receive the contrast agent gadolinium (exclusions follow):
* No history of untreatable claustrophobia
* No presence of metallic objects or implanted medical devices in body (i.e., cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants)
* No history of sickle cell disease
* No contraindication to intravenous contrast administration
* No known allergy-like reaction to gadolinium or moderate or severe allergic reactions to one or more allergens as defined by the American College of Radiology (ACR); patient may be eligible if willing to undergo pre-treatment as defined by the institution's policy and/or ACR guidance
* No findings consistent with renal failure, as determined by glomerular filtration rate (GFR) \< 30 mL/min/1.73 m\^2 based on a creatinine level obtained within 28 days prior to registration
* Weight lower than that allowable by the MRI table
* No prior MRI of study breast within the 12 months prior to registration
* Non-pregnant and non-lactating. Patients of child-bearing potential must have a negative pregnancy test within 7 days prior to registration. Perimenopausal patients must be amenorrheic \> 12 months to be considered not of child-bearing potential
* ≥ 18 years of age
* Signed study-specific informed consent prior to registration
* Pathologically confirmed diagnosis of breast cancer, clinical stage I-II (T1-3 N0 M0, T0-2 N1 M0). Diagnosis must be by needle biopsy; patients diagnosed by surgical excision are excluded.
* Patients must have either:
* Estrogen receptor (ER) negative/progesterone receptor (PR) negative (\< 10% by immunohistochemistry IHC staining) and HER-2 negative breast cancer OR
* ER negative/PR negative (\< 10% by IHC staining) and HER-2 positive tumors
* HER-2 status will be determined as per the 2013 ASCO CAP guidelines:
* HER-2 is considered positive if there is IHC 3+ staining or ISH positive using either single probe ISH or dual probe ISH
* HER-2 is considered negative if there is IHC 0 or 1+ staining or ISH negative using either single probe ISH or dual probe ISH
* No patients with previous ipsilateral invasive breast cancer or ductal carcinoma in situ (DCIS)
* No patients with bilateral breast cancer
* No patients with known deleterious mutations in breast cancer (BRCA) genes
* No current history of receiving hormonal therapy, tamoxifen, and or aromatase inhibitors for therapeutic measures
* No history of chemotherapy for cancer within 6 months prior to registration
* No patients scheduled to receive neoadjuvant chemotherapy or partial breast irradiation following breast conserving surgery
* Eligible for BCT based on clinical examination, mammography and, if standard practice at a given institution, ultrasound and/or tomogram. Women who cannot be appropriately selected for BCT based on these standard imaging studies, and for whom additional imaging is recommended to clarify local disease extent, will not be eligible for this trial.
* No patients with multicentric or multifocal disease scheduled to undergo multiple lumpectomies. Multifocal disease that can be encompassed in a single operative bed can be enrolled.
* Suitable to undergo MRI and receive the contrast agent gadolinium (exclusions follow):
* No history of untreatable claustrophobia
* No presence of metallic objects or implanted medical devices in body (i.e., cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants)
* No history of sickle cell disease
* No contraindication to intravenous contrast administration
* No known allergy-like reaction to gadolinium or moderate or severe allergic reactions to one or more allergens as defined by the American College of Radiology (ACR); patient may be eligible if willing to undergo pre-treatment as defined by the institution's policy and/or ACR guidance
* No findings consistent with renal failure, as determined by glomerular filtration rate (GFR) \< 30 mL/min/1.73 m\^2 based on a creatinine level obtained within 28 days prior to registration
* Weight lower than that allowable by the MRI table
* No prior MRI of study breast within the 12 months prior to registration
* Non-pregnant and non-lactating. Patients of child-bearing potential must have a negative pregnancy test within 7 days prior to registration. Perimenopausal patients must be amenorrheic \> 12 months to be considered not of child-bearing potential
* ≥ 18 years of age
* Signed study-specific informed consent prior to registration
Gender
Female
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01805076
Org Class
Other
Org Full Name
Alliance for Clinical Trials in Oncology
Org Study Id
A011104
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Effect of Preoperative Breast MRI on Surgical Outcomes, Costs and Quality of Life of Women With Breast Cancer
Primary Outcomes
Outcome Measure
Local-regional recurrence (LRR)
Outcome Time Frame
Up to 5 years
Secondary Ids
Secondary Id
ACRIN 6694
Secondary Id
U10CA037447
Secondary Id
NCI-2012-02045
Secondary Outcomes
Outcome Time Frame
Up to 5 years
Outcome Measure
Re-operation rate
Outcome Time Frame
Within the first 6 months
Outcome Measure
Conversion rate to mastectomy secondary to persistent positive margins or poor cosmesis
Outcome Time Frame
Up to 5 years post-randomization
Outcome Measure
Time to contralateral breast cancer
Outcome Time Frame
Up to 5 years post-randomization
Outcome Measure
Disease-free survival (DFS)
Outcome Time Frame
Up to 5 years post-randomization
Outcome Measure
Overall survival
Outcome Time Frame
Up to 5 years post-randomization
Outcome Measure
Breast cancer specific survival will be measured
Outcome Time Frame
Up to 5 years
Outcome Measure
Rate of MRI-guided localization assisted surgery (Arm B)
Outcome Time Frame
Up to 5 years
Outcome Measure
False positive rate for MRI detection of multiple disease foci
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Locked Fields
Render the field
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Caren Greenstein
Investigator Email
cgreenstei@wphospital.org