Rapid Access to Contrast-Enhanced spectral mammogRaphy (RACER): a more efficient work-up of women recalled from breast cancer screening

Approximately 70% of all recalls from our breast cancer screening program are
*false-positives* (FPs). These FPs generate (unnecessary) patient anxiety and
health care costs. For this population, a new breast imaging tool,
contrast-enhanced spectral mammography (CESM) showed to be an excellent
problem-solving tool. In CESM, a dual-energy mammography is performed after
administration of iodine-based contrast. After image acquisition, a radiologist
will read two different images per breast and per projection view: one
low-energy image (which is similar to a regular mammogram) and one recombined
image, which shows areas of contrast enhancement. The added information of
contrast capturing lesions increases the diagnostic performance compared to
conventional mammography, increasing both cancer detection (sensitivity) and
reducing false-positive findings (increased specificity).
In current standard care, women recalled from screening for a suspicious breast
lesion first visit their general practitioner (GP) and then a hospital*s breast
nurse/surgeon before visiting a radiologist. Hence, many recalled women visit
various physicians unnecessarily, since disease prevalence in this population
is only 30%. Since sensitivity of full-field digital mammography (FFDM)
decreases in dense breasts and general specificity of FFDM is limited, many
women are undergoing follow-up even when the initial work-up did not detect any
malignancies. Consequently, a rapid access to a more accurate breast imaging
modality (i.e. CESM) should in theory be more accurate, more patient friendly
and cost-efficient.

The RACER project studies a more efficient approach based on (rapid access to)
CESM, primarily resulting in less follow-up exams due to the superior
specificity of CESM over FFDM. In addition, otherwise occult cancers will be
detected in the women undergoing CESM, since it*s sensitivity is slightly
higher. In this study, women are directly recalled for CESM. If this exam is
negative, women are immediately reassured by the radiologist. Only if an
abnormality remains suspicious on CESM women will undergo further tissue
sampling and referral to a breast cancer clinic. Consequently, rapid access to
CESM is more accurate, will lead to less unnecessary imaging, interventions or
follow-up, is more patient-friendly and is less expensive than current usual
care.

Multicenter, randomized controlled clinical trial.

For the intervention group, rapid access to CESM is guaranteed. Prior to the
exam, a questionnaire will be used to screen for risk factors for using
iodine-based contrast agents (this is common practice in many Radiology
departments). In a typical CESM exam, a intravenous catheter is placed in
antecubital vein and two minutes prior to image acquisition the contrast agent
is administered (Ultravist 300 or Xenetix 300, 1.5 mL/kg body weight, flow rate
3 mL/s, followed by saline flush). Then, mammography images are acquired of
both breasts in two standard projection views, with additional views being
requested by the radiologist on call when deemed necessary (the imaging
protocol is similar to common clinical practice). The image acquisition with
the breast compressed in mammography paddles can sometimes be painful, but the
additional time for the acquisition of a CESM image is only max. 4 seconds for
a single exposure. After completion of the exam, the intravenous catheter is
removed.
The most common diagnoses in recalled women are: (1) cysts, (2)superimposition
of glandular tissue mimicking breast cancer, (3) benign lesions, or (4) breast
cancer or ductal carcinoma in situ. Final diagnosis or outcome is acquired as
follows (per diagnostic category and with bypassing visits to breast clinic in
most cases): (1) CESM showing a so-called *eclipse sign*, pathognomonic for
cysts; (2) a negative CESM exam with no suspect lesion on both low-energy and
recombined image; (3) CESM exam, including targeted ultrasound, and core biopsy
or fine needle cytology aspiration for pathological diagnosis; (4) like group
3. Since many false-positive recalls are caused either by cysts or by
superimposition densities, CESM prevents many unnecessary additional exams or
biopsies. In scenario*s 1 and 2, a minimum of one doctor visit (breast clinic)
would become unnecessary, whilst the omission of follow-up strategies such as
breast MRI or follow-up visits after 6 or 12 months will result in saving
another 1 to 2 doctor visits in scenario 2. The most important strength of the
investigated intervention is the reduction of false positive findings and the
number of unnecessary doctor visits. A second advantage of offering rapid
access to CESM in recalled women is the slightly higher accuracy of CESM for
detecting breast cancer.

During the CESM exam patients will undergo a venous puncture for the i.v.
catheter. The administration of contrast can sometimes results in warm
sensations, a strange taste in the mouth or nausea. These complaint usually
resolve spontaneously within 30 seconds. Undergoing a mammographic exam can be
painful for some women, but the additional compression time for CESM is max. 4
seconds longer, making the discomfort of the compression comparable to standard
mammography.
Patients allocated to the experimental (CESM) study arm will receive a slightly
increased radiation dose (ca. 2.8 mGy versus normally 1.6 mGy per exposure).
The use of iodine-based contrast agents could result in a hypersensitivity
reaction or in severe cases even anaphylatic shock. I taan also cause a often
self-limiting decreased renal function. However, the risks of these CESM
disadvantages are very limited (<1%).