Feasibility of 3D Breast Ultrasound in comparison with 3D breast MRI
Amendement: Analysis of false positive rate with 3D ultrasound

Over the last decades there has been a steady increase in incidence of breast
cancer in women. With an incidence of breast cancer in 2005 of 12 to 13% in
general population in The Netherlands, breast cancer is the single most
diagnosed cancer in women(1). Modalities currently used in breast imaging are
mammography, hand-held ultrasound and magnetic resonance imaging (MRI). MRI is
nowadays regarded as gold standard in breast imaging with high sensitivity
(91-100%)(2,3,4). However a limited specificity of 72% is reported in a
meta-analysis due to enhancement of benign lesions(5). Other drawbacks of MRI
are the limited availability, relatively long examination time, higher costs
and in 10% of patients MRI cannot be performed due to claustrophobia(6) or
contraindications (e.g. implantable cardioverter defibrillator)(7,8).
Ultrasound (US) is cost-effective, lacks radiation, readily available and well
tolerated by patients. Currently a radiologist or technologist using a
hand-held transducer carries out a 2D US examination. Only impressions are
caught and stored in a PACS. This manual scanning is time-consuming and
operator dependent. Modern volumetric viewing and batch reading of 2D US images
are not possible. Operator dependency and interobserver variability are
disadvantages of 2D US. In several studies with women at risk of developing
breast cancer 2D US seemed better to equal in comparison to mammography(9-13).
A promising new technique is 3D US or ABVS (automated breast volume scanning)
(14,15). The ACUSON S2000* Automated Breast Volume Scanner (Siemens, Erlangen)
has been cleared for commercialization by the US Food and Drug Administration
(FDA) and will be used in accordance with its cleared labeling. In contrast to
hand-held 2D US, is ABVS operator independent and standardized acquisition is
possible by a radiologist or an instructed technician. The 3D US data sets can
be stored in PACS and are available for interpretation on a workstation. Also
correlation with other available examinations such as mammography and 3D MRI
becomes possible. As 3D images can be archived and viewed later, reliable
comparison with previous examinations becomes feasible. These are regarded as
major steps forward in making ultrasound less operator dependent and thus
suitable for follow-up and screening. First experience with 3D whole breast
ultrasound shows another promising advantage: image reconstructions in planes
perpendicular to the transducer can reveal spiculated patterns surrounding
malignant lesions that are well known as specific signs of cancer in
mammography. Such patterns could not be observed well or were completely absent
in 2D US(16). The purpose of this study is to assess the feasibility of 3D US
in comparison with 3D MR imaging as gold standard and mammography and 2D US

Primary Objective: Examining the value of ABVS in relation to current breast
imaging techniques by: - comparison of ABVS findings with MRI findings. -
comparison of ABVS findings with mammography and hand-held US. Secondary
Objectives: - assessment of operator dependency of ABVS data acquisition. -
assessment of tolerability of ABVS image acquisition - assessment of
interobserver variability of ABVS data interpretation. -
Amendement: Analysis of the false positive rate in patients with low a priori
change of having breast cancer.

General A prospective study design will be used to assess reproducibility of
image acquisition and the feasibility and accuracy of breast tumor detection
with ABVS in patients scheduled for breast MRI. All participants receive
written information and need to sign an IRB-approved informed consent prior to
inclusion. An ABVS examination will be carried out and will be interpreted
within 1 week prior or following MRI. The interpreters are blinded for the MRI
findings. Imaging findings will be compared with MRI findings and if available
also with surgical and histopathological findings. Imaging study MRI The
examination will be carried out with a 1.5T MRI scanner (General Electric:
Signa) using a routine screening protocol. The patients is positioned in the
prone position. A a dedicated bilateral multi-element breast surface coil is
used. The MRI examinations are performed 5 - 15 days after the first day of the
last menstrual period. Indication for MRI are high risk patients, pa(General
Electric Signa 1,5T) tients with dense breast tissue with inconclusive prior
examination, evaluation of suspected or histological proven malignancy,
preoperative evaluation of lesion size, multifocality and multicentricity,
follow-up of patients with a treatment regiment with neo-adjuvant therapy and
patients with breast implants. ABVS All subjects will be examined with 3D ABVS
(ACUSON S2000*: Automated Breast Volume Scanner, Siemens). ABVS imaging
acquisition is restricted to 3 examiners (an experienced mammoradiologist (MJCM
Rutten, MD, PhD) and two radiology residents (I. Dubelaar,MD and M. de
Jong,MD).
Amendement: MAMMOGRAPHY: The examination will be performed by dedicated
technicians in breast imaging with a mammography unit (Mammomat inspiration,
Siemens).

The use of ultrasound in breast imaging is not associated with any know
hazards. the extra burden for the patients will be the exam itself, total
acquisition time takes 10 minutes. The Greatest benefit of the exam is expected
if a new lesion is found only on 3D ABVS imaging, and cancer is detection only
with 3D ABVS. As a negative side effect, is an expected increase in needle
biopsies. If there are abnormalities visualised only on the ABVS image data,
that are not visible with or not reported with the other imaging studies the
following will be undertaken; - If a lesion has a typical benign appearance
(BIRADS 2), no further steps are taken. - If a lesion is probably benign
(BIRADS 3) or possibly / probably malignant (BIRADS 4 or 5) the patient will be
contacted; targeted hand-held US will be advised and when considered necessary
a biopsy specimen will be taken. Prior to inclusion all participants are
informed about this possibility, the procedure and the risks of this procedure
(attached to this file as a separate document).