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
Conditions
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.
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.
Interventions
Sponsors
Study design
Eligibility
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Local-regional Recurrence (LRR) | Up to 5 years |
Secondary
| Measure | Time frame |
|---|---|
| Re-operation Rate | Up to 5 years |
| Conversion Rate to Mastectomy Secondary to Persistent Positive Margins or Poor Cosmesis | Within the first 6 months |
| Time to Contralateral Breast Cancer | Up to 5 years post-randomization |
| Disease-free Survival (DFS) | Up to 5 years post-randomization |
| Overall Survival | Up to 5 years post-randomization |
| Breast Cancer Specific Survival Will be Measured | Up to 5 years post-randomization |
| Rate of MRI-guided Localization Assisted Surgery (Arm B) | Up to 5 years |
| False Positive Rate for MRI Detection of Multiple Disease Foci | Up to 5 years |
Countries
United States
Contacts
M.D. Anderson Cancer Center
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 59 years |
| Axillary Surgery ALND only | 6 Participants |
| Axillary Surgery Both | 14 Participants |
| Axillary Surgery Neither | 4 Participants |
| Axillary Surgery Patient did not have surgery | 7 Participants |
| Axillary Surgery SLN biopsy only | 143 Participants |
| Clinical N stage N0 | 151 Participants |
| Clinical N stage N1 | 10 Participants |
| Clinical T stage T1 | 230 Participants |
| Clinical T stage T2 | 46 Participants |
| Clinical T stage T3 | 2 Participants |
| Did patient get systemic chemo? No | 32 Participants |
| Did patient get systemic chemo? Patient did not have surgery and did not have systemic chemo | 7 Participants |
| Did patient get systemic chemo? Yes | 272 Participants |
| Did patient have adjuvant RT? Missing | 7 Participants |
| Did patient have adjuvant RT? No | 44 Participants |
| Did patient have adjuvant RT? Yes | 125 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 280 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants |
| HER2 status Negative | 126 Participants |
| HER2 status Positive | 32 Participants |
| HER2 status Unknown | 1 Participants |
| Initial or Delayed Mastectomy Delayed | 4 Participants |
| Initial or Delayed Mastectomy Initial | 10 Participants |
| Initial or Delayed Mastectomy Patient did not have mastectomy | 137 Participants |
| Initial or Delayed Mastectomy Patient did not have surgery | 21 Participants |
| Margin Status < 2mm | 73 Participants |
| Margin Status >= 2mm | 205 Participants |
| Margin Status Patient did not have surgery | 21 Participants |
| Margin Status Positive (tumor at surgical margin) | 10 Participants |
| Mastectomy? No | 271 Participants |
| Mastectomy? Patient did not have surgery | 14 Participants |
| Mastectomy? Yes | 27 Participants |
| Mastectomy Side Bilateral | 14 Participants |
| Mastectomy Side Patient did not have mastectomy | 137 Participants |
| Mastectomy Side Patient did not have surgery | 14 Participants |
| Mastectomy Side Unilateral | 6 Participants |
| Max lesion size (cm) | 1.3 cm |
| Menopausal Status Peri | 6 Participants |
| Menopausal Status Post | 130 Participants |
| Menopausal Status Pre | 34 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 46 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 12 Participants |
| Race (NIH/OMB) White | 195 Participants |
| Receiving or recently completed neoadjuvant chemotherapy ? No | 130 Participants |
| Receiving or recently completed neoadjuvant chemotherapy ? Yes | 31 Participants |
| Reoperation? No | 129 Participants |
| Reoperation? Patient did not have surgery | 7 Participants |
| Reoperation? Yes | 14 Participants |
| Sex: Female, Male Female | 158 Participants |
| Sex: Female, Male Male | 0 Participants |
| Total number of lesions identified 1 | 140 Participants |
| Total number of lesions identified 2 | 25 Participants |
| Total number of lesions identified 3 | 2 Participants |
| Total number of lesions identified 4 | 2 Participants |
| Type of initial breast surgical procedure performed Initial BCS | 134 Participants |
| Type of initial breast surgical procedure performed Initial bilateral mastectomy | 9 Participants |
| Type of initial breast surgical procedure performed Initial mastectomy | 9 Participants |
| Type of initial breast surgical procedure performed Patient did not have surgery | 7 Participants |
| Was ultrasound performed? Missing | 7 Participants |
| Was ultrasound performed? No | 3 Participants |
| Was ultrasound performed? Yes | 148 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 13 / 158 | 12 / 161 |
| other Total, other adverse events | 26 / 158 | 28 / 161 |
| serious Total, serious adverse events | 0 / 158 | 1 / 161 |