Diffusion Weighted MR Imaging of the Breasts in Women at High Risk of Breast Cancer: A Pilot Study

Enrollment and Recruitment:

A total of 100 high-risk women will be enrolled in this pilot study. High-risk for this
study is defined as women at significantly increased risk of breast cancer. The
Investigators will use the American Cancer Society Guidelines for Breast Screening with MRI
as adjunct to mammography [2]. These guidelines recommend annual screening mammography for
high risk women including BRCA mutations, first-degree relative of BRCA carrier, lifetime
risk 20-25% or greater, previous history of chest radiation age 10 to 30 years and other
syndromes related to increased breast cancer risk. We also included women with a history of
previous high risk breast lesion(s) such as atypical hyperplasia, lobular carcinoma in situ
or atypical lobular hyperplasia and a personal history of breast cancer by clinical
consensus.

Patients who have been scheduled for the study will be contacted by research staff by phone
to ask if they would be interested in participating in a research study. A script will be
used to determine if patient is interested in hearing about a research study, if not the
call will be discontinued immediately. If yes, more details will be provided to the patient
to make a determination if they would like to participate.

If the patient is interested, she will be asked to come into the UNC MRI Department one hour
prior to her scheduled MRI appointment. On the day of her MRI study, the patient will meet
with the study coordinator or other assigned listed study personnel and will consent the
subject to this study. Research coordinator/listed study personal will go through the
consent form with the patient and answer any questions she may have. If patient agrees to
participate after review of consent form, the patient will sign and date, the coordinator
will then sign and date and patient will be formally enrolled. The patient will then undergo
her ordered clinical breast MRI followed by one diffusion weighted MRI sequence.

Imaging Procedure: Each eligible patient, who provides consent for the study, will undergo a
MR imaging screening questionnaire. If the patient has no contraindications, an intravenous
line will be placed into a vein in the patient's arm and the patient will be placed prone
with her breasts in a dedicated MRI breast coil. The patient will be given earplugs to
decrease the noise level while in the magnet during the 45 minute total time period.
High-resolution MRI sequences of the breasts and axillary regions will be performed before
and after a gadolinium-DTPA bolus injection as per ordered clinical breast MRI protocol.
Afterwards, one diffusion-weighted (DW) MRI sequence of the breast(s) will be performed. The
DW sequence takes approximately 90 seconds.

The clinical images will be interpreted as per clinical protocol. The clinical radiologists
will not have DW images to interpret. Therefore, it will not influence clinical decision
concerning therapy.

Needle Core Biopsy/Surgery: All patients who are recommended for a needle core biopsy or
open surgical biopsy for a breast lesion from their clinical Breast MRI will be scheduled by
their surgeon. The radiologist performing the MRI-guided needle core biopsy or the surgeon
performing the open surgical biopsy will be blinded to the results of the DW imaging, and
therefore it will not influence clinical decision concerning therapy.

Reader Study: Five readers, radiologists that are experts in breast imaging and who are
blinded to the study results, will be given de-identified MRI and DWI MRI images from the
patient's entry MRI (MRIe) study and 1-year follow-up MRI (MRIf) study. Study radiologist
data sheets will be completed for each study. The reader will have to complete the data
sheets for MRIe before he/she can read and evaluate MRIf. The readers are blinded to the
pathologic data at all times. For each condition MRIe and MRIf, each reader will check one
of the checkboxes of each query that presents the lesion type (mass or non-mass
enhancement), anatomic location (upper outer, upper inner, lower outer, lower inner or
subareolar), largest dimension in centimeter, signal intensity on T1- and T2-weighted images
(high, iso- or low to the fibroglandular tissue), morphology such as shape (round, oval,
lobulated or irregular) and margin(smooth, irregular or spiculated) for mass, distribution
(focal, linear, ductal, segmental or regional) for non-mass enhancement, enhancement pattern
(homogeneous, heterogeneous, rim enhancement, dark internal septations, enhancing internal
septations or central enhancement for mass; homogeneous, heterogeneous, stippled/punctate,
clumped or reticular/dendritic for non-mass enhancement) and kinetic curve patterns on
contrast-enhanced MRI (persistent, plateau or washout), signal intensity on DWI MRI /ADC map
(high, iso-, low to the fibroglandular tissue) and an ADC value marked through quantitative
analysis on the DWI study. The readers will assign any lesion(s) as benign, probably benign,
suspicious and highly suggestive of malignancy according to the imaging findings and decide
the probability of malignancy in percentages on contrast-enhanced MRI and DWI MRI,
independently for the entry and final MRI study. After each radiologist reader has completed
the data sheets for each patient, the data will be entered into a secure data base for
statistical analysis.

Inclusion Criteria

1. Women at high-risk of breast cancer with an order for a clinical screening breast
MRI.

2. Asymptomatic women.

3. Able to provide informed consent.

4. At least 21 years of age.

Exclusion Criteria

1. Women with symptom such as palpable mass or nipple discharge.

2. Women with MRI/MRA contraindications such as a cardiac pacemaker, and aneurysm clip,
cochlear implants, and metal in the eyes.

3. Women who have had a moderate or severe contrast reaction to intravenous
gadolinium-DTPA.

4. Women who are not able to give consent.

5. Women diagnosed with breast cancer within the last 6 months.

6. Women who are pregnant.

7. Male patients.