MRI and Mammography Before Surgery in Patients With Stage I-II Breast Cancer

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.

- 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