Women with dense breast tissue are at a disadvantage. Compelling
evidence shows that density in the highest quartile represents a 4- to
6-times higher risk of breast cancer.1 This is coupled with
the fact that when mammography is the only screening test performed,
sensitivity decreases by 10% to 20% for women with dense breasts.2
circumstances have prompted a push for supplementary screening tests.
Twelve states now have breast density inform legislation, and new bills
are being drafted in many more states. All of the states with breast
density laws require facilities to send a post-exam letter to women with
dense breasts alerting them that the condition can interfere with the
effectiveness of a mammogram.
These laws have potentially
enormous implications that may result in a significant increase in
supplementary screening with technologies, such as ultrasound (US),
magnetic resonance imaging (MRI), tomosynthesis, molecular breast
imaging (MBI), and spectral imaging.
Mammography: Benefits and limitations
benefits of mammographic imaging are well established. Screening
mammography can help reduce deaths from breast cancer among women ages
40 to 70.
However, screening mammograms miss about 20% of breast cancers present at screening.3 The main cause of these false-negative results is high breast density,3 which is usually collectively referred to as fibroglandular tissue.4 A phenomenon known as masking, in which the surrounding dense breast tissue obscures a cancer, may occur during mammography.
medical evidence shows that masses in women with dense breast tissue
are more likely to be cancerous and their masses are less likely to be
detected under standard imaging. It is a real dilemma for these women—on
the one hand they are at greater risk, and on the other, there is less
likelihood that their cancer will be detected,” said Richard Frank, MD,
PhD, CMO, Siemens Healthcare.
As such, researchers have suggested
that reliable and reproducible breast density measurements are a
prerequisite for the use of breast density to monitor primary prevention
strategies and for the use of mammographic density to define women at
higher breast cancer risk who would benefit from intensified early
detection and surveillance protocols.6
Breast density legislation gains momentum
response to the limitations of mammography to detect cancers in women
with dense breasts, several states have adopted laws requiring referring
physicians to notify patients when the interpreting radiologist
determines that their pattern of fibroglandular tissue is considered
As approximately 50% of women undergoing screening
mammography are classified as having either “heterogeneously dense” or
“extremely dense” breasts,5 breast density notification legislation could have significant impact on overall patient care.
of the challenges with such a law, however, is the language in the
notification varies across states, which can impact the quality of care
delivered. Additionally, insurance coverage for supplemental screening
is not part of the mandate. Only one state, Connecticut, requires
insurers to cover additional screenings under its notification law.
Therefore, while some patients will be able to afford additional
screening, others clearly will not.
Dr. Frank believes there
should be a national standard for breast cancer notification. “It is
this variability across state bills that is a problem and argues in
favor of a federal solution or single national program perhaps channeled
by way of the Mammography Quality Standards Act (MQSA),” he said.
more states implement the law, the mandate is gaining momentum on the
national stage. On January 18, 2011, federal legislation for dense
breast notification was introduced in Congress, but it has yet to be
enacted. Also, the U.S. Food and Drug Administration (FDA) is
considering adding a breast-density reporting amendment to the MQSA.
This means that women would receive standardized nationwide notification
about their breast tissue density after their mammograms. The FDA said
it would consider the proposed rule in December 2013.7
of a federal mandate point to the benefits of early detection and
long-term reduced costs. “The benefits of early detection will offset
the initial costs. Earlier detection leads to better efficacy,
preservation of anatomy, and it is also less expensive,” pointed out Dr.
Yet opinions are mixed among radiologists. While many
believe information is power, there are many unanswered questions. For
example, what impact could breast density notification have on patient
care, and should such notification become mandatory without clinical
research to back it up? Furthermore, how practical is the law if it does
not require supplemental imaging to be covered by insurance?
think it does help a significant number of women who otherwise might not
be told of their breast density, and that they could have some
additional screening with ultrasound. But I think it’s very important
that, in conjunction with the legislation, there be a funding mandate so
that people are not left in the position of wanting an exam because
they have been told by the physician that it would be good for them, yet
not be covered by the insurance carriers,” said Laurie Margolies, MD
FACR, Associate Professor of Radiology, Department of Radiology, Chief
of Breast Imaging, Dubin Breast Center, Mount Sinai School of Medicine,
New York, NY.
“We really have to ensure that if there is mandated
information, that there will be mandated requirements for coverage of
these additional modalities as there is in CT,” noted Rachel Brem, MD,
Professor of Radiology and Vice-Chair of Radiology, The George
Washington University School of Medicine and Health Sciences.
Breast ultrasound (US): The next test
Although there are several adjunct tests to mammography, US is most often indicated due to its accessibility and low cost.
recent study concluded that technologist-performed handheld screening
breast US offered to women in the general population with dense breasts
can aid detection of small mammographically occult breast cancers
(cancer detection rate, 0.8-10 cancers per 1000 women screened).8
2-dimensional mammography falls short, US can help because it acquires
images differently from x-ray systems. “Ultrasound can separate masses
from dense tissue, which in certain cases you cannot make any
distinction, especially with extremely dense tissue. It’s essentially a
white out; you can’t pick out mass from background dense tissue. So
that’s where US really shines. It also helps to distinguish between
something solid from something cystic, especially when there is a new
nodule,” said Dr. Justin S. Torok, Diagnostic Radiologist, Women’s
Imaging Specialist, Heritage Valley Health System, Beaver, PA.
automated breast ultrasound systems (ABUS) have been introduced. These
include the somo-v ABUS, which has been acquired by GE Healthcare
(Waukesha, WI), and the ACUSON S2000™ Automated Breast Volume Scanner
(ABVS) from Siemens Healthcare (Malvern, PA) (Figure 1).
technician has positioned the transducer, these US systems
automatically scan the whole breast, capturing multiple ultrasound
images and instantly generating a 3-dimensional (3D) visualization.
somo-v ABUS is the only US system to receive FDA 510(k) approval for
breast cancer screening as an adjunct to mammography for asymptomatic
women with dense breast tissue.
“If you look at the cancers
detected with mammography and look at those detected by ABUS, the
cancers detected by ABUS are node negative, small invasive breast
cancers—exactly those cancers that you are trying to detect,” said Dr.
A key shortcoming in conventional breast US is that it is
usually used to evaluate a small area surrounding a palpable mass or a
specific mammographic finding.10 “ABVS surveys both breasts
and is a complete scan,” said Dr. Torok. “If there is an abnormality in a
far lateral or a high superior position, the technician can include the
tissue in the scan. We can detect more lesions and smaller lesions
because you get better separation of lesions from background tissue, so
when you’re looking at cancers down to 3 mm size, they are easier to
identify on the S2000 than on the conventional US units that we had.”
Brem added, “This is really a leap forward in how we screen
intermediate risk women in order to find additional cancers. We have
very high-risk women who benefit from breast MRI, but how do we screen
for women with intermediate risk of breast cancer where mammography can
be less optimal?”
drawback of US for breast screening is that it is labor intensive and
too time-consuming to accommodate a high-volume screening environment.
While automated breast US is not going to replace mammography, it
simplifies and expedites volume acquisition for consistent results,
thereby improving workflow.
“ABUS whole-breast imaging can be
easily integrated in the screening environment,” indicated Dr. Brem. “US
is not translatable unless it’s automated because of screening workflow
issues. It takes 19 minutes for a technologist to manually screen using
US, but it doesn’t take any time to screen with ABUS because it is
automated. Now with ABUS, you only need a trained person who can acquire
the image dataset, then the entire dataset can be interpreted by a
Similarly, automated breast US plays an important role
at Heritage Valley Health System, where Dr. Torok and staff recently
adopted the ACUSON S2000. The system acquires a series of consecutive
B-mode pictures and reconstructs 3D data sets of the entire breast
volume. ACUSON S2000 offers applications for fatty tissue imaging,
elasticity imaging, and biopsies with US guidance.
will call patients direct from a screen where you have an extremely
dense mammogram from the patient’s baseline study. 3D US is recommended
to take a closer look at each breast as sort of a baseline US. We are
trying to do it on every case with a category 5 suspicious cancer so we
get used to seeing what cancers look like on the 3D US. What I like most
about it is on the coronal, MIP reconstructed image, architectural
distortion comes out looking pretty well—it almost comes out looking
like a breast MRI,” said Dr. Torok.
The advantage of automation to
diagnostic accuracy and workflow is significant. There is greater
consistency with the automated as opposed to the manual ultrasound
“Because ABVS is automated there is less variation with
the technologists performing the exam, which gives you a more consistent
exam and exam time across all technologists,” indicated Beverly
Feragotti, Radiology Operations Manager for Women’s Health, Heritage
Valley Health System. This level of reproducibility is important for the
radiologist when comparing currents and prior diagnostic studies.
with most diagnostic imaging technologies, US has advantages and
disadvantages. The disadvantage with breast US is that it may lead to
additional tests. “Supplemental US screening increases cancer detection
beyond mammography alone, but may also result in an increased number of
additional tests,9” said Richard G. Barr, MD, PhD, professor
of radiology at the Northeast Ohio Medical University in Youngstown, OH,
in a recent study11 on screening breast US.
find some cancers that mammography has missed, but it is operator
dependent, and there is a significant number of false positives leading
to many benign biopsies and a lot of anxiety,” said Dr. Margolies.
Dr. Torok noted, “On a routine basis, especially with whole-breast US,
you’ll find some new lesions, and you may have to do a biopsy or MRI to
follow up. With 3D US, we will encounter a large number of lesions that
we did not see on a mammogram. Although most will be malignant, we have
to make a decision whether or not to follow them up or to do a biopsy.
It’s information that’s good to have and increases sensitivity for
picking up a tumor, but there are a lot of other benign things you have
to sort through to get to that end point,” indicated Dr. Torok.
a breast density notification law could actually enhance workflow at
Heritage Valley Health System. “If in Pennsylvania we did get breast
density notification legislation, it would permit doing these as a
screening study or at least as an adjunctive screening study. We could
then do exams in batches, which would be much more efficient,” said Dr.
Similar to US, contrast-enhanced
breast MR imaging frequently reveals mammographically occult cancers.
Screening breast MRI has been shown to substantially increase the rate
of cancer detection; however, it is much less common than breast US.
Based on the American Cancer Society (ACS) guidelines,12 breast MRI is recommended as an adjunctive screening tool to mammography12
only in patients at very high risk for breast cancer—such as those with
an estimated lifetime risk of 20% to 25%, patients with a BRCA
mutation, those with a nontested first-degree relative who is a BRCA
carrier, and those who received radiation therapy to the chest between
the ages of 10 and 30 years.
Compared to mammography and US,
the sensitivity of contrast-enhanced breast MRI in cancer detection is
considerable at > 94%,, and specificity ranging from 37% to 97%.13
dedicated MRI systems offer proven advantages. The first FDA approved
MRI device designed specifically for breast imaging is the Aurora 1.5T
Dedicated Breast MRI System by Aurora Imaging Technology Inc. A recent
study showed that the system led to better sensitivity, specificity,
negative predictive value, positive predictive value, and
receiver-operating characteristic area than has been historically
reported in trials for breast MRI on whole-body MRI scanners.14
Sentinelle Breast MRI coil system, provides a Variable Coil Geometry
that transforms MRI systems into dedicated systems for breast MR imaging
The MAGNETOM Espree - Pink uses the Sentinelle
Vanguard for Siemens coil solution, which makes imaging and biopsies
possible using only a single coil. Enhanced image quality is obtained
through an improved signal-to-noise ratio and with the help of eight RF
channels. In addition, some GE Healthcare and Toshiba breast MRI units
leverage the Sentinelle Breast MRI coil system on their breast MRI
As with US, MRI should be used as a complement to, not
instead of, screening mammography. Although an MRI is a more sensitive
test, it may still miss some cancers that a mammogram would detect.15
breast density notification laws ramp up the numbers of patients with
dense breast seeking adjunct breast MRI procedures? It is questionable,
since reimbursement as an adjunct test to mammography is limited to
high-risk patients. “Only people who have ≥ 20% lifetime risk of breast
cancer will get the extra screening with MRI; otherwise, they will get
an ultrasound for supplemental screening,” said Dr. Margolies, adding
that MRI has other drawbacks. “There are a significant number of false
positives, it’s a costly procedure, and a time-intensive procedure and
uncomfortable for patients. Yet it is exquisitely sensitive,” indicated
Dr. Brem points out that breast-specific gamma
imaging (BSGI), can be used as a supplemental test to mammography,
offers comparable sensitivity to MRI, and is far less expensive.
works equally well in women with dense breasts and nondense breasts. It
is less common, but it is at least equally effective as the other
modalities. If we are comparing MRI and BSGI, we have shown that the
sensitivity is equal on MRI and BSGI, but the specificity is better with
BSGI,” said Dr. Brem. “It’s also important to remember if you go with
the physiological imaging approach, 15% to 20% of patients can’t have an
MRI because they have an implantable device, are too large, have renal
deficiency, or are claustrophobic.”
Up-and-coming solutions: Tomosynthesis and spectral imaging
evolving technologies that support lesion detection in patients with
dense breasts are breast tomosynthesis and spectral imaging.
tomosynthesis, which creates a 3D rendering of the entire breast,
combined with conventional 2D mammography, is highly indicated for
patients with dense breast tissue. The ability to review images slice by
slice allows breast tissue to be displayed with less tissue
superimposition compared to 2D mammography. This demonstrates true
lesions much more clearly. A recent study compared screening recall
rates and cancer detection rates of tomosynthesis plus conventional
digital mammography to those of conventional digital mammography alone.
Researchers found that the addition of tomosynthesis reduced recall
rates for all breast density and patient age groups, with significant
differences found for scattered fibroglandular, heterogeneously dense,
and extremely dense breasts.16
study concluded that combining mammography with tomosynthesis in
a screening environment resulted in a significantly higher cancer
detection rate and enabled the detection of more invasive cancers.17
breast tomosynthesis is widely used in Europe, Selenia Dimensions from
Hologic Inc. (Danbury, CT) is the first, and currently only, FDA-cleared
system indicated for breast tomosynthesis. According to the literature,18
Hologic’s system has a higher cancer detection rate than conventional
digital mammography and improves the radiologists’ confidence to
significantly reduce recall rates.19
recently submitted its premarket approval application (PMA1) to the FDA
for its breast tomosynthesis solution, an add-on option to the
Senographe Essential unit, to generate 3D digital breast tomosynthesis
images for screening and diagnosis of breast cancer. According to Pilar
Anton Serrano, Global Communications Manager, GE Healthcare, the
company’s goal is to gain FDA approval for a single 3D MLO view as a
replacement for the current 2-view mammography done in 2D. “With
GE’s Breast Tomosynthesis, a single MLO view will provide clinical
noninferiority (as measured by ROC analysis) compared to a 2-view
digital mammography exam—at half the dose and with just one compression.
This solution has the potential to replace digital mammography exams in
screening to help radiologists detect breast cancer,” said Ms. Anton
For now, tomosynthesis used with routine mammography is
not a substitute for additional screening with ultrasound or MRI, said
“With tomosynthesis there has been a decrease in
the callback rates, and clearly there are some cancers that we have seen
on the tomosynthesis that we haven’t seen on the 2D mammogram. There is
a benefit to using tomosynthesis with 2D over just using 2D mammography
alone,” said Dr. Margolies.
Spectral imaging on digital mammography
technology designed to enhance the detection of lesions in dense
breasts is single-shot spectral imaging. Earlier this year, Philips
(Andover, CT) received 510(k) clearance from the FDA for its MicroDose
SI system, the first full-field digital mammography (FFDM) system on the
market with the capability to enable future single-shot spectral
imaging applications. Single-shot spectral imaging is built upon the
premise that breast density comprises different tissue types and
materials that absorb x-rays at various energies. The technology
powering the MicroDose SI uses this fundamental behavior of x-rays,
allowing clinicians to see more than just a shadow in mammogram images
by separating high- and low-energy x-ray within one exposure. What is
unique about spectral imaging is that it will generate quantitative
breast density data.
“This new innovation with MicroDose
technology will give quantitative breast density information with
low-dose data, which will be incredibly valuable for radiologists to
apply to their reports, particularly when reimbursement is tied to
performance,” said Raymond Tu, MD, FACR, Chairman, Department of
Radiology, NFPHC/United Medical Center, Washington, DC.
Dr. Tu is
looking forward to updating single-shot spectral imaging on its existing
MicroDose digital mammographic system (Figure 2), a low-dose
mammography system built on photon counting technology.
The impact of legislation on care
important is breast density notification legislation? While there is
ample evidence that supplemental tests often detect cancers that
screening mammography misses, the verdict is still out on how breast
density notification legislation will impact patient care.
believes “whole breast US and breast MRI is going to be important, and
all of these adjunct risk factors are something that patients should
know, and that [dense breast awareness] will emphasize very diligent
clinical screening and careful clinical follow up.” However, he also
offers caution with respect to the dangers of a federal mandate. “To
make it a rule is questionable because breast density is very subjective
in a lot of ways, and how it’s going to play out long term depends on
how it is truly measured, and if it’s accurate. At the same time, we
don’t want to alarm people unnecessarily and give them unnecessary tests
when their real true risk is much lower,” said Dr. Tu.
there is no proven correlation between breast-density notification and
improved patient outcomes, breast density notification legislation
continues to gain momentum and, for some, shows promise.
is an important and powerful tool, and the more we know about our
health care, the better advocates we can be for ourselves,” said Dr.
Brem. “Perhaps, a federal regulation is a way to ensure that all women
in our country are informed of what their breast density is, and
hopefully, along with that strategy, it will improve breast cancer
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