With new laws on breast-density notification sweeping the nation,
radiologists are concerned 2-dimensional (2D) digital mammography alone
may not be enough for screening patients with dense breasts.
Subsequently, many breast-imaging centers are looking to expand their
arsenal of screening technologies.
Some of these
adjunct-screening tools include automated breast ultrasound (ABUS),
tomosynthesis, opto-acoustic imaging, breast magnetic resonance imaging
(MRI), and molecular breast imaging (MBI). Each imaging device offers an
additional or alternative view that may detect lesions in the breast
that might otherwise go unnoticed.
Dense breast awareness
is well established that mammographic breast density—a reflection of
the proportions of fat, connective tissue, and epithelial tissue in the
breast—is a risk factor for breast cancer. A recent study found women
with dense tissue in 75% or more of the breast have a risk of breast
cancer 4 to 6 times as great as the risk among women with little or no
A study by doctors at Harvard Medical
School and Brigham and Women’s Hospital, Boston, MA, and colleagues,
found higher mammographic density is associated with more aggressive
tumor characteristics and also with in situ tumors.2 The
authors wrote: “masking of a tumor can occur because cancerous tissue
and mammographically-dense tissue have similar x-ray attenuation,
allowing tumors to go undetected on screening mammography examination
and progress to a more advanced and aggressive stage before detection.”
They recommended “breast density should be included in risk prediction
models across tumor subtypes.”
These and other studies on
mammography screening for women with dense breasts have catalyzed a
movement for dense breast awareness. Earlier, growing concern over the
efficacy of mammograms on women with dense breasts had prompted
Connecticut to enact a law in 2009 requiring that women be informed of
their breast density when they receive their mammography reports.
Related legislation in the same state mandates that insurance companies
provide coverage for comprehensive ultrasound screening of an entire
breast or breasts if a mammogram demonstrates heterogeneous or dense
breast tissue based on the Breast Imaging Reporting and Data System
(BI-RADS) established by the American College of Radiology (ACR).3 Since then, several others states have enacted similar breast- density notification laws.
Mammograms plus adjunct exams
estimated 40% of all women undergoing screening mammography have dense
breasts, according to the American College of Radiology Imaging Network
“There is the issue of masking breast cancer
because of the density of the breast. Everyone agrees there is greater
risk for breast cancer
in women with dense breasts,” said Dennis McDonald, Medical Director for
breast imaging for the Sutter Medical Center Sacramento,
To address the problem, the center implemented
Volpara objective breast-density measurement software, a breast-density
assessment tool designed to improve early detection among women with
Volpara automatically generates objective,
automatic measurement of volumetric breast density values under the
Volpara Density Grade (VDG®), a grading system that
correlates with the American College of Radiology BI-RADS Density
Grading Classifications. Volpara is FDA cleared for all digital
mammography units, and integration with other digital mammography
systems, CAD systems, and mammography reporting solutions are also
“We purchased the Volpara software to give a more
objective estimation of the breast density because it’s a volumetric
measurement. In our experience, there is really good correlation with
our visual interpretation; it lent some consistency to the whole process
of density determination,” said Dr. McDonald.
as such a large percentage of the screening population has dense or
heterogeneous breast tissue, many radiologists believe mammography for
those patients should be followed up with an adjunct imaging test, such
as ultrasound or MRI.
A recent trial by ACRIN5 reported
that there is a significant breast cancer detection benefit of
supplementing annual mammography screening with ultrasound in women at
elevated risk due to dense breast tissue. The same study also found that
a single screening MRI following 3 years of annual mammography and
ultrasound screenings identified additional cancers.
other studies confirm that mammography fails to see about half of the
cancers present in women with dense breasts. These women tend to be
diagnosed with more advanced cancers often detected clinically in the
interval between annual mammography screenings,” said Wendie Berg, MD,
PhD, and Professor of Radiology at the University of Pittsburgh School
of Medicine, Magee-Womens Hospital of UPMC, Pittsburgh, PA, and the
trial’s principal investigator.
She noted, “For women who have
dense breasts, adding ultrasound to mammography will increase the chance
of finding invasive cancer before it spreads to lymph nodes,” said Dr.
Currently, there is only
one ultrasound system approved in the United States for breast cancer
screening as an adjunct to mammography
for asymptomatic women with > 50% dense breast tissue and no prior
breast interventions. This system, the somo•v® Automated
Breast Ultrasound (ABUS) (recently acquired by GE Healthcare) has made
significant improvements in the visualization of cancer-hiding tissue in
“Mammography is an effective tool at finding
breast cancer, but it doesn’t work equally well in everyone,” noted
Rachel F. Brem, MD, Director, Breast Imaging and Interventional Center,
Professor of Radiology, Vice Chair, Research and Faculty Development,
The George Washington University Medical Center, Washington, DC. Dr.
Brem was the principal investigator of the SOMO-INSIGHT clinical study
examining whether full-field digital mammography along with the somo•v
could improve breast cancer detection when compared to mammography alone
in women with dense breasts.
“In recently completed studies
demonstrated with the addition of somo•v ABUS, we find about 30% more
cancers in women who have a normal mammogram, normal physical
examination, and dense breasts. For the > 40% of women who have dense
breasts, this is a significant advancement in their breast healthcare,”
said Dr. Brem.
She added, “What ABUS does is solves the problem of how to find cancer in dense breasts and at an earlier stage.”
new breast-density legislation is adopted nationwide, increasing
numbers of women with dense breasts will require ultrasound screenings
in addition to mammography. The challenge in the clinical setting is how
to streamline the process. The standard procedure today is to use hand
held ultrasound, which is very operator dependent. Comparatively,
automated breast ultrasound systems lend themselves better to the
screening environment, according to Dr. Brem.
With somo•v ABUS,
the scanner is positioned on the breast and the technologist presses a
button to begin a 3-dimensional (3D) ultrasound scan of the front,
outer, and inner sides of the breast. Siemens Healthcare also offers an
automated ultrasound, the ACUSON S2000™ Automated Breast Volume Scanner
In a new study, Marcela Böhm-Vélez, MD, of Weinstein
Imaging Associates in Pittsburgh,
PA, and Ellen B. Mendelson, MD, a Diagnostic Radiologist at Northwestern
Memorial Hospital, Chicago, IL, are using the ABVS for screening and
comparing hand held with automated breast ultrasound. The design of the
study is to show that they can detect as many lesions with the ABVS
system as with hand held ultrasound.
“With 40% to 50% of the
population with dense breasts, there are not enough trained sonographers
available to do breast ultrasound for all of these women. That is why
hand held ultrasound would be a good option for screening all of these
women with dense breasts without requiring a technologist there doing
it,” said Böhm-Vélez. “We hope that this technology could replace hand
held ultrasound, especially for the screening patient.”
important feature with ABVS is the additional coronal view. “The ABVS
technology provides the coronal view, which we can’t view with hand held
ultrasound, and the coronal view better shows the pulling of the
Cooper’s ligaments, which is an indirect sign that there may be a cancer
there,” said Böhm-Vélez. “Since you have 3D reconstruction, you can
look at images from any view—coronal, transverse, longitudinal, whatever
you want—instead of looking at 2D static images with the hand held
She added, “I think for a large screening program,
there is a role for this technology, especially for women with dense
Opto-acoustic imaging: A new angle on ultrasound
new approach to ultrasound is opto-acoustic imaging technology, which
is designed to improve accuracy. Opto-acoustic imaging technology
combines optical imaging with ultrasound to provide blood maps of the
body. It uses very short pulses of laser light directed at the region of
interest, which are converted into a real-time image. The colors
(wavelengths) of the light pulses are chosen due to their ability to be
preferentially absorbed either by oxygenated blood or by deoxygenated
blood. The acoustic waves that result from the light absorption travel
to the transducers. By using this array of transducers, it is possible
to reconstruct 2D images.
“The difference in frequency that the
ultrasound wave sends back depends on the characteristics of that
tissue. When tissue has cancer, one of the hallmarks of cancer is that
it does not regulate blood flow well because it uses up large amounts of
oxygen,” explained Mike Ulissey, MD, a medical consultant to Seno
Medical Instruments Inc., San Antonio, TX.
“Using laser light at
different frequencies, we can also co-register it with ultrasound
imaging so that the radiologist can look at the lesion and identify its
location, and use the laser wavelength from opto-acoustic imaging to
analyze that specific mass or region of concern. With ultrasound, it
looks at structural information, evaluating the morphology of the lesion
at the margins.”
Opto-acoustic imaging can be used not only for cancer detection but also to analyze a potentially suspicious breast lump.
opto-acoustic imaging is a functional technology, it is similar to MR
spectroscopy and hybrid positron emission tomography / computed
tomography (PET/CT) in that it provides functional and anatomical data
with what seems to be a similar level of accuracy. However, we
anticipate it will be less expensive and will not use radiation,
radioisotopes, and no contrast agents,” said Dr. Ulissey.
Combo-mode imaging with tomosynthesis
of the most logical extensions of 2D mammography is 3-dimensional
mammography, or breast tomosynthesis. While breast tomosynthesis has
been in use in Europe for several years, it only recently became
available for breast screening in the U.S., opening up new possibilities
for women with dense breasts.
Hologic Inc.’s Selenia Dimensions
3D mammography system, the first device of its kind to receive FDA
510(k) clearance, is indicated for diagnostic performance. Technologists
can use a one-touch control to transition between imaging modes: FFDM
(2D imaging), tomosynthesis (3D imaging), or “combo-mode” imaging (2D+3D
imaging). The latter feature quickly acquires a digital mammogram and a
tomosynthesis scan in the same compression (a screening exam consists
of a digital mammogram and breast tomosynthesis image set).
recent study analyzed results from 12,631 examinations interpreted by
using mammography alone and mammography plus tomosynthesis. Researchers
found that with mammography plus tomosynthesis there was a 31% increase
in the cancer detection rate; the false-positive rate was 13% less; and
there was a 26% increase in the detection of higher-grade cancers.6
another study, led by Liane Philpotts, MD, Chief of Breast Imaging at
the Yale University School of Medicine, New Haven, CT, investigators
concluded that adding 3D to a screening exam reduced recall rates by
“With Hologic’s 3D technology, we can see the
entire breast more clearly in 1-mm slices,” said Dr. Philpotts. “This
allows us to find additional cancers earlier and also dismiss ambiguous
spots that are actually normal breast tissue.”
Roles of breast MRI and MBI
MRI is the gold standard for acquiring functional data for high-risk
patients with dense breasts and patients with a strong family or genetic
history (BRCA1 or BRCA2 genes) of breast disease. Although breast
MRI is not a routine screening procedure, the study led by Dr. Berg5 found MRI detected additional invasive cancers not seen on mammography or ultrasound.
there has been criticism of breast MRI for its high false-positive
rates, resulting in unnecessary biopsies, surgical procedures, and
anxiety for the patient. “Those false-positive rates are higher in
conventional breast MRI systems than in dedicated breast MRI units,”
said Alan Hollingsworth, MD, Medical Director, breast surgeon at Mercy
Women’s Center at Mercy Health Center, Oklahoma City, OK.
In a recent multi-center trial,8
managed by ACR Image Metrix (the American College of Radiology’s
clinical research organization), Dr. Hollingsworth and other researchers
found that dedicated breast MR systems led to better diagnostic
performance for sensitivity, specificity, negative predictive value,
positive predictive value, and area under the receiver operating
characteristic curve than what has been reported for breast MR imaging
on conventional breast MRI systems.
“False-positive rates from
previously reported trials using whole-body breast MRI have typically
been between 30% to 50%. The dedicated breast MRI system offers a
significant improvement in performance,” noted Dr. Hollingsworth. “Even
within the 93 false positives, 27% were high-risk histologies, for which
excision is often recommended.8 This kind of performance
should provide breast radiologists and surgeons alike with a higher
level of diagnostic confidence, and could have significant impact on the
role of breast MRI.”
While most conventional MRI systems have
special coils for breast imaging, there is only one FDA-approved MRI
device designed specifically for breast imaging. The unit is the Aurora
1.5T Dedicated Breast MRI System with Bilateral SpiralRODEO, and it was
the MRI system used in the study. The low frequency of false-positive
and false-negative findings associated with this dedicated breast MRI
system may allow for use of breast MRI with low-risk patients in both
the screening and diagnostic environments.
Where does MBI fit in?
the widespread availability of breast MRI, many radiologists may be
wondering where MBI fits in. Much like breast MRI, MBI is a tool that is
a supplement to mammography. But where MBI is especially useful in the
clinical setting is for imaging patients who cannot have an MRI.
In the study led by Dr. Berg,5
she noted, “MRI detected additional invasive cancers not seen on
mammography or ultrasound; however, we found that MRI was significantly
less tolerable than mammography or ultrasound for many study
participants. Of those participants offered an MRI, only 58% accepted
Similarly, for patients at Karmanos Cancer
Center, Detroit, MI, problems with undergoing MRI were the impetus for
seeking out a solution in terms as a multidisciplinary approach to
breast cancer. For Sharon Helmer, MD, clinical Service Chief, Imaging
Department, and Director, Breast Imaging, Karmanos Cancer Center, 2 key
scenarios encouraged her to consider MBI for screening her patients.
wanted to use another tool to examine their breasts with MR to see
beyond mammography and ultrasound. But I practice with an urban
population with rising obesity rates, and we found a significant number
of patients who are candidates for MRI, but couldn’t have MRI for
various reasons: renal function, implants or pacemakers, claustrophobia,
and weight issues,” explained Dr. Helmer. “We were interested in MBI
because about 20% of our patients are high-risk patients with dense
breasts, who would normally get a biopsy and an MR for extent
While the center has a dedicated 3.0T MR, for a
large number of patients, doctors could not provide surgeons with
additional metabolic information for treatment planning. Therefore,
doctors at Karmanos Cancer Center advocated for MBI as a solution, and
implemented the Discovery* NM750b, a dual-head CZT unit by GE
Healthcare. The CZT detectors fit into a compact device, allowing users
to image the breast up close, right up to the chest wall. In a recent
study,9 comparing performance characteristics of dedicated
dual-head gamma imaging and mammography in screening women with
mammographically dense breasts, researchers found that the addition of
gamma imaging to mammography significantly increased detection of
node-negative breast cancer in dense breasts by 7.5 per 1000 women
screened (95% CI: 3.6, 15.4). However, to be clinically important, gamma
imaging will need to show equivalent performance at decreased radiation
doses. Regarding radiation, Dr. Helmer points out that recent low-dose
protocols developed by the Mayo Clinic have helped in safely conducting
“The unit provides high-resolution imaging, and
great functionality, and the patients are really comfortable walking
into a room that looks very much like a mammogram unit. Also, there is
very minimal compression of the breast, and the responses from patients
have been very positive,” said Dr. Helmer.
Both MRI and MBI are
indicated for patients who have extremely dense breasts or have a strong
family history of breast cancer. According to Dr. Helmer, MRI and MBI
serve very similar functions. “MR gives you exquisite anatomic detail,
but MBI also captures clear, precise images, even for those with dense
breast tissue,” she said.
“Obviously, MR gives you chest wall
information in addition to the liver, which we can’t get with MBI. As a
radiologist, you look at all the film. You’re not seeing the full extent
of the anterior lungs and upper part of the liver that you would be
able to include in your assessment on an MR. If the patient has an
invasive carcinoma, the patient will be assessed and staged with CT and
other exams,” said Dr. Helmer.
But she noted that one of the
unexpected benefits of MBI is that it is very good for lobular
carcinoma. “That’s good because often it’s difficult to determine the
exact extent of disease of a lobular carcinoma on a mammogram and
ultrasound. Yet, unlike MRI, MBI is safe for those who have pacemakers,
metal implants or other foreign bodies, and patients with renal
challenges,” she said.
Dr. Helmer believes MBI fits into the
niche that complements mammography and ultrasound, and like breast MRI,
provides data on the metabolic activity of an abnormality in the breast
or an area of interest that may be of concern.
mammography, MBI allows better detection of very small lesions in women
with dense breast tissue. Not only will this help eliminate false
positives, it may help to detect breast cancers earlier when the disease
is highly survivable,” she said. “It’s not a replacement of
mammography, but it does offer us another a chance to look at a patient
with dense breasts or other problems with the breast. It’s another tool
in our armamentarium, and it gives us data, much like MRI.”
also useful for following up response to noeadjuvent chemotherapy.
“Sometimes when you follow patients with mammography or ultrasound to
see response to their chemotherapy, the tumor may not appear that
different size-wise because we are not able to really assess how it’s
responding to the chemotherapy. Whereas with MRI and MBI, we can see
that it is less vascular, and that it is responding to the chemotherapy.
MBI is a more cost-effective way to do that
follow-up,” she said.
For Dr. Helmer and the other radiologists at
Karmanos Cancer Center, MBI is another tool in their imaging arsenal
that enables them to offer more diagnostic and therapeutic services and
to give patients more choices for better care.
Today, mammography remains the first line of defense for detecting breast cancer in its earliest stages.
is important to emphasize that an annual mammogram is still recommended
and neither ultrasound nor MRI is meant to replace mammography,”
remarked Ellen Mendelson, MD, co-investigator and Lee F. Rogers
Professor of Radiology at the Feinberg School of Medicine, Northwestern
University, Chicago, IL.
Nonetheless, there are limitations to 2D
mammography, and supplemental ultrasound and MRI screening help detect
more cancers, as do tomosynthesis and MBI, when combined with
With the growing trend in patient advocacy
extending the conversation on breast screening into the public domain,
radiologists are responding by expanding their portfolio of imaging
services. As such, there is an important role adjunct technologies will
play in the future of breast screening.
- Boyd NF, Guo H, Martin LJ, et al. Mammographic density and the risk and detection of breast cancer. N Engl J of Med. 2007;356:227-236M.
- Yaghjyan L, Colditz GA, Collins LC, et al. Mammographic breast
density and subsequent risk of breast cancer in postmenopausal women
according to tumor characteristics. J Natl Cancer Inst. 2011;103:1179-1189. doi: 10.1093/jnci/djr225. Epub 2011 Jul 27.
- Are you dense? http://www.areyoudense.org/. Accessed Feb. 4, 2013.
- Stomper PC, D’Souza, DJ, DiNitto PA, Arredondo MA. Analysis of parenchymal density on mammograms in 1353 women 25-79 years old. AJR Am J Roentgenol. 1996;167:1261-1265.
- Berg WA, Zhang Z, Lehrer D, et al. Detection of breast cancer with
addition of annual screening ultrasound or a single screening MRI to
mammography in women with elevated breast cancer risk. JAMA. 2012;307:1394-1404. doi:10.1001/jama.2012.388.
- Skaane P, Gullien R, Eben EB, et al. Reading time of FFDM and
tomosynthesis in a population-based screening program. Radiological
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- Philpotts, L, Raghu, M, Durand, M, et al. Yale University School of
Medicine. Initial experience with digital breast tomosynthesis in
screening mammography. Presented May 3, 2012 at American Roentgen Ray
Society Annual Meeting.
- Hillman BJ, Harms SE, Stevens G, et al. Diagnostic performance of a dedicated 1.5-T breast MR imaging system. Radiology. 2012;265:51-58.
- Rhodes DJ, Hruska CB, Phillips SW, et al. Dedicated dual-head gamma
imaging for breast cancer screening in women with mammographically dense
breasts. Radiology. 2011 Jan;258(1):106-118. doi: 10.1148/radiol.10100625. Epub 2010 Nov 2.