Studies Support Breast Ultrasound for Screening

A pair of new research studies offers guidance on when and where to use ultrasound for breast screening. The publications highlight the important advances being made in one of radiology’s most versatile modalities. 

Ultrasound is used in developed countries for supplementary breast cancer screening in women who may not be suitable for X-ray-based mammography due to issues like dense breast tissue.

  • Ultrasound is also being examined as a primary screening tool in developing regions like China and Africa, where access to mammography may be limited.

But despite growing use, there are still many questions about exactly when and where ultrasound is best employed in a breast screening role – and this week’s studies shed some light. 

First up is a study in Academic Radiology in which researchers compared second-look ultrasound to mammography in women with suspicious lesions found on breast MRI. 

  • Their goal was to find the best clinical path for working up MRI-detected lesions without performing too many unnecessary biopsies. 

In a group of 221 women, second-look ultrasound was largely superior to mammography with… 

  • Higher detection rates for mass lesions (56% vs. 17%).
  • A much higher detection rate for malignant mass lesions > 10 mm (89%).
  • But worse performance with malignant non-mass lesions (22% vs. 38%).

They concluded second-look ultrasound is a great tool for assessment and biopsy of MRI-detected lesions > 10 mm without calcifications. 

  • It’s not so great for suspicious non-mass lesions, which might be better sent to mammography for further workup. 

Breast ultrasound of non-mass lesions was also the focus of a second study, this one published in Radiology

  • Non-mass lesions are becoming more frequent as more women with dense breast tissue get supplemental screening, but incidence and malignancy rates are low. 

So how should they be managed? In a study of 993 women with non-mass lesions found on whole-breast handheld screening ultrasound, researchers classified by odds ratios the factors indicating malignancy…

  • Associated calcifications (OR=21.6).
  • Posterior shadowing (OR=6.9).
  • Segmental distribution (OR=6.2).
  • Mixed echogenicity (OR=5.0).
  • Larger size (2.6 vs. 1.9 mm).
  • Negative mammography (2.8% vs. 29%).

The Takeaway

Ultrasound’s value comes from its high prevalence, low cost, and ease of use, but in many ways clinicians are still exploring its optimal role in breast cancer screening. This week’s research studies should help.

ABUS Flies Solo for Breast Screening

Is breast ultrasound ready for use as a primary breast screening modality – without mammography? Maybe not in developed countries, but researchers in China gave automated breast ultrasound a try, with results that are worth checking out in a new study in AJR

Mammography is unquestionably the primary imaging modality for first-line breast screening, with other technologies like ultrasound and MRI taking a supplemental role, such as for working up questionable cases or for women with dense breast tissue.

  • But the standard mammography-dominated paradigm might not be suitable for some resource-challenged countries that have yet to build an installed base of X-ray-based mammography systems. 

One of these countries is China, which not only has fewer mammography systems in rural areas but also has a population of women who have denser breast tissue, which can cause problems with conventional mammography. 

  • As a result, the Chinese National Breast Cancer Screening Program has adopted ultrasound as its primary screening modality, with women ages 35-69 eligible for screening breast ultrasound every 2-3 years. Mammography is reserved for additional workup. 

But handheld ultrasound has challenges of its own. It’s operator-dependent, and image interpretation requires experienced radiologists – also in short supply in some Chinese regions.

  • So the AJR researchers performed a study of 6k women who were screened with GE HealthCare’s Invenia ABUS 2.0 scanner, which uses ultrasound to scan women lying in the supine position. Images were sent via teleradiology to expert radiologists at a remote institution.

How did ABUS perform as a primary screening modality? The researchers found that after a single round of screening …

  • ABUS had a cancer detection rate of 4.0 cancers per 1k women (4.4 for women 40-69).
  • Sensitivity was 92% and specificity was 88%.
  • Abnormal interpretation rate was 12%.
  • 96% of detected cancers were invasive, and 74% were node-negative.
  • Two interval cancers were detected (rate of 0.33 per 1k).

How do the numbers compare to mammography? 

  • The cancer detection rate in the Breast Cancer Surveillance Consortium study was 5.1 cancers per 1k women, so not far off. 

The Takeaway

The results offer an interesting look at an alternative to the mammography-first breast screening paradigm used in developed countries, where ABUS is mostly used as a supplemental technology. For resource-challenged areas around the world, ABUS with teleradiology could solve multiple problems at once.

The Cost of Extra Cancer Detection

It’s well known that using additional screening modalities beyond traditional 2D mammography can detect more cancers in women with dense breast tissue. But at what cost? A new study in Clinical Breast Cancer documents both the clinical value and the economic cost of supplemental breast imaging technologies. 

2D mammography is the basis for any breast cancer screening program, but the modality’s shortcomings are well known, especially in women with dense breasts. 

  • In fact, the FDA earlier this month began requiring breast imaging providers to notify women of their density status and explain how higher density is a breast cancer risk factor. 

Imaging vendors and clinicians have developed a range of technologies to supplement 2D mammography when needed, ranging from DBT to molecular breast imaging to breast MRI.

  • Each has its own advantages and disadvantages, which can leave many breast imaging providers confused about the best technology to use.

To shed some light, Matthew Covington, MD, of the University of Utah compared detection rates for various supplemental imaging modalities; he then estimated costs for each if it was the only modality used for supplemental imaging with 2D mammography in a U.S. population with 469k detectable breast cancers. 

  • The study assumed that 2D mammography would detect only 41% of cancers – leaving the majority undetected. 

Adding a supplemental modality boosted cancer detection rates, but also screening’s cost …

  • DBT detected 47% of all cancers at a cost of $933M
  • Ultrasound detected 51% at a cost of $1.84B
  • MBI detected 71% at a cost of $4.16B
  • Contrast-enhanced mammography detected 80% at a cost of $3.87B
  • MRI detected 100% at a cost of $6.36B

As the data indicate, MRI is clearly the most effective supplemental modality, but at a cost that’s almost 7X that of DBT. 

The Takeaway

The new data are a fascinating – if sobering – look at the intersection of clinical value and economic cost. They also highlight healthcare’s inconvenient truth: The resources needed to provide the highest-quality care are finite, regardless of whether you’re in a single-payor or fee-for-service system.

Why the FDA’s Density Rule Matters

The FDA’s new rules on reporting breast density to women getting mammograms went into effect on September 10. The implementation has been expected for some time, but this week’s rollout generated a wave of positive press coverage that highlights the importance both of breast density awareness and of breast screening.

The FDA in March 2023 said it would implement a national standard requiring providers to inform women of their breast density, which can obscure lesions on conventional X-ray mammography. 

  • Breast density is also a risk factor for cancer, and patient advocacy groups had been pressuring the FDA to set a standard to replace what has become a patchwork of state-by-state notification rules. 

The FDA’s rules have been incorporated into the Mammography Quality Standards Act, and require that … 

  • Mammography reports include a plain-language patient summary with “an overall assessment of breast density.” 
  • The summary must include specific language that defines breast density, explains its ramifications for detection and cancer risk, and suggests the need for additional imaging tests.

A novel aspect of the new rules is that they were mostly driven by patients – women like JoAnn Pushkin and the late Nancy Cappello who as patients discovered first-hand the shortcomings of X-ray-based mammography for women with dense breast tissue. 

What’s next? Density-awareness proponents are now turning their attention to reimbursement, which for supplemental imaging is inconsistent across the U.S.

  • A fix for the problem – the Find It Early Act – is working its way through Congress, and women’s health advocates lobbied on Capitol Hill this week to try to push the legislation through before the end of the current Congressional session. 

The new reporting landscape also creates opportunities for better software tools to detect and manage breast density and better predict risk in patients with dense breast tissue. 

  • Clinicians already realize that women with dense breasts not only need different screening modalities like MRI and ultrasound, but that they might also require more frequent screening due to their heightened cancer risk. 

The Takeaway

The FDA’s new breast density rules matter for a variety of reasons, from showing the power of patients to change their imaging experience to outlining a future in which risk plays a more prominent role in breast screening. While more work remains to be done, this is a good time to savor the triumph.

US + Mammo vs. Mammo + AI for Dense Breasts

Artificial intelligence may represent radiology’s future, but for at least one clinical application traditional imaging seems to be the present. In a new study in Radiology, ultrasound was more effective than AI for supplemental imaging of women with dense breast tissue. 

Dense breast tissue has long presented problems for breast imaging specialists. 

  • Women with dense breasts are at higher risk of breast cancer, but traditional screening modalities like X-ray mammography don’t work very well (sensitivity of 30-48%), creating the need for supplemental imaging tools like ultrasound and MRI.

In the new study, researchers from South Korea tested the use of Lunit’s Insight MMG mammography AI algorithm in 5.7k women without symptoms who had breast tissue classified as heterogeneously (63%) or extremely dense (37%). 

  • AI’s performance was compared to both mammography alone as well as to mammography with ultrasound, one of the gold-standard modalities for imaging women with dense breasts. 

All in all, researchers found …

  • Mammography with AI had lower sensitivity than mammography with ultrasound but slightly better than mammography alone (61% vs. 97% vs. 58%)
  • Mammography with AI had a lower cancer detection rate per 1k women but higher than mammography alone (3.5 vs. 5.6 vs. 3.3)
  • Mammography with AI missed 12 cancers detected with mammography with ultrasound
  • Mammography with AI had the highest specificity (95% vs. 78% vs. 94%)
  • And the lowest abnormal interpretation rate (5% vs. 23% vs. 6%)

The results show that while AI can help radiologists interpret screening mammography for most women, at present it can’t compensate for mammography’s low sensitivity in women with dense breast tissue.

In an editorial, breast radiologists Gary Whitman, MD, and Stamatia Destounis, MD, observed that supplemental imaging of women with dense breasts is getting more attention as the FDA prepares to implement breast density notification rules in September. 

  • They recommended follow-up studies with other AI algorithms, more patients, and a longer follow-up period. 

The Takeaway

As with a recent study on AI and teleradiology, the current research is a good step toward real-world evaluation of AI for a specific use case. While AI in this instance didn’t improve mammography’s sensitivity in women with dense breast tissue, it could carve out a role reducing false positives for these women who get mammography and ultrasound.

US Tomo for Dense Breasts

What’s the best way to provide supplemental imaging when screening women with dense breasts? A new study this week in Radiology offers support for a newer method, whole-breast ultrasound tomography. 

It’s well-known by now that dense breast tissue presents challenges to traditional X-ray-based mammography.

  • In fact, mammography screening’s mortality reduction is far lower in women with dense breasts compared to nondense breasts (13% vs. 41%). 

A variety of alternative technologies have been developed to provide supplemental imaging for women with dense breasts, from handheld ultrasound to breast MRI to molecular breast imaging. 

  • One supplemental technology is whole-breast tomography, developed by Delphinus Medical Technologies; the firm’s SoftVue 3D system was approved by the FDA in 2021 as an adjunct to full-field digital mammography for screening women with dense breast tissue. 

With SoftVue, women lie prone on a table with the breast stabilized in a water-filled chamber that provides coupling of sound energy between the breast and a ring transducer that scans the entire breast in 2-4 minutes.

  • Unlike handheld ultrasound, the scanner provides volumetric coronal images that provide a better view of the fat-glandular interface, where many cancers are located.

SoftVue’s performance was analyzed by researchers from USC and the University of Chicago in a retrospective study funded by Delphinus. 

  • They performed SoftVue scans along with digital mammography on 140 women with dense breast tissue from 2017 to 2019; 36 of the women were eventually diagnosed with cancer. 

In all, 32 readers interpreted the scans, comparing the performance of FFDM with ultrasound tomography to FFDM alone, finding … 

  • Better performance with FFDM + ultrasound tomography (AUC=0.60 vs. 0.54)
  • An increase in sensitivity in women with mammograms graded as BI-RADS 4 (suspicious), (37% vs. 30%) 
  • No statistically significant difference in sensitivity in BI-RADS 3 cases (probably benign), (40% vs. 33%, p=0.08)
  • A mean of 3.3 more true-positive and 0.9 false-negative findings per reader with ultrasound tomography, a net gain of 2.4

The Takeaway

The findings indicate that ultrasound tomography could become a new supplementary tool for imaging women with dense breasts. They are also a shot in the arm for Delphinus, which as a smaller vendor has the challenge of competing with large multinational OEMs that also offer technologies for supplemental breast screening. 

Fine-Tuning AI for Breast Screening

AI has shown in research studies it can help radiologists interpret breast screening exams, but for routine clinical use many questions remain about the optimal AI parameters to catch the most cancers while generating the fewest callbacks. Fortunately, a massive new study out of Norway in Radiology: Artificial Intelligence provides some guidance. 

Recent research such as the MASAI trial has already demonstrated that AI can help reduce the number of screening mammograms radiologists have to review, and for many low-risk cases eliminate the need for double-reading, which is commonplace in Europe. 

  • But growing interest in breast screening AI is tempered by the field’s experience with computer-aided detection, which was introduced over 20 years ago but generated many false alarms that slowed radiologists down. 

Fast forward to 2024. The new generation of breast AI algorithms seems to have addressed CAD’s shortcomings, but it’s still not clear exactly how they can best be used. 

  • Researchers from Norway’s national breast screening program tested one mammography AI tool – Lunit’s Insight MMG – in a study with data obtained from 662k women screened with 2D mammography from 2004 to 2018. 

Researchers tested AI with a variety of specificity and sensitivity settings based on AI risk scores; in one scenario, 50% of the highest risk scores were classified as positive for cancer, while in another that threshold was set to 10%. The group found …

  • At the 50% cutoff, AI would correctly identify 99% of screen-detected cancers and 85% of interval cancers. 
  • At the 10% cutoff, AI would detect 92% of screen-detected cancers and 45% of interval cancers 
  • AI understandably performed better in identifying false-positive cases as negative at the 10% threshold than 50% (69% vs. 17%)
  • AI had a higher AUC than double-reading for screen-detected cancers (0.97 vs. 0.88)

How generalizable is the study? It’s worth noting that the research relied on AI of 2D mammography, which is prevalent in Europe (most mammography in the US employs DBT). In fact, Lunit is targeting the US with its recently cleared Insight DBT algorithm rather than Insight MMG. 

The Takeaway

As with MASAI, the new study offers an exciting look at AI’s potential for breast screening. Ultimately, it may turn out that there’s no single sensitivity and specificity threshold at which mammography AI should be set; instead, each breast imaging facility might choose the parameters they feel best suit the characteristics of their radiologists and patient population. 

USPSTF’s Mammography Letdown?

Last year’s relief that the USPSTF would lower its recommended starting age for breast screening to 40 gave way to frustration this week that the group did not go farther in its final decision on mammography recommendations. 

In a series of papers in JAMA journals this week, the USPSTF tackled a range of breast screening issues, from the age at which screening should start to whether modalities like ultrasound and MRI should be used to supplement conventional mammography.

That was the good news. The bad news is that breast screening advocates mostly got shut out on a variety of other issues, with the USPSTF … 

  • Advising that breast screening be conducted biennially (every two years), rather than annually as most women’s imaging advocates would prefer
  • Declining to raise the recommended upper limit for screening from 74 to 79
  • Declining to recommend supplemental screening with MRI or ultrasound for women with dense breast tissue, even as women express frustration with the lack of reimbursement for these exams

On the positive side, the USPSTF finally weighed in on DBT, stating that the 3D mammography technology is equivalent to digital mammography for breast screening. 

  • But in another disappointment, the group said it couldn’t find any studies stating that DBT was better than 2D digital mammography. 

Given the fierce battles that have been fought over screening guidelines in the last 15 years, what made the USPSTF change its mind on mammography’s starting age? 

  • One big factor is the 2% annual rise in breast cancer incidence in women in their 40s from 2015 to 2019; the higher mortality rates among Black women was another issue (see story below in The Wire).

The Takeaway

The USPSTF’s move to lower its recommended starting age for screening mammography is a welcome – if overdue – change for women, who for 15 years have borne the brunt of the group’s conservative approach to guideline formation. The question remains, is the USPSTF making the same mistake all over again when it comes to supplemental imaging and annual screening? And how long will women have to wait this time until it sees the light?

When Access to Screening Isn’t Enough

A new study published this week in JAMA Network Open indicates that – even when women have access to breast screening – other factors can limit mammography’s life-saving impact. Researchers found that women with more unmet social needs had lower breast screening rates and higher rates of advanced disease – even if they had access to a mammography center. 

Research into social determinants of health – the racial, demographic, and environmental factors that can affect the quality of a person’s health – have gained steam in the last several years.

In the new study, researchers noted that unmet social needs can include housing instability, social isolation, food insecurity, and transportation challenges, and these needs can occur even in high-income areas with access to screening mammography. 

  • They studied the issue in Miami-Dade County, Florida, where all women 200% below the poverty line have access to no-cost screening mammography at safety net hospitals – in theory removing cost as a barrier to breast screening.

Researchers studied 336 women who filled out a survey on social needs; of these, 62% self-identified as Hispanic, 19% as Black, and 19% as White, and 76% had screening mammograms. Researchers found a lower odds ratio for getting a mammogram due to …

  • An increasing number of unmet social needs (OR=0.74)
  • Increasing age at diagnosis (OR=0.92)

Patients were also more likely to present with late-stage disease if they …

  • Had two or more unmet social needs (33% vs. 18%)
  • Had problems with their home utilities (17% vs. 5%) or childcare access (12% vs. 3%)
  • Were presenting to a safety net hospital (31% vs. 18%)

The authors noted that although no single unmet social need was found to have a statistically significant impact on screening mammography rates, multiple needs piling up could “overwhelm” patients so they can’t find the time to schedule preventive health check-ups. 

The Takeaway

The new findings offer a more complex view of breast screening disparities beyond just access to mammograms. Public health authorities and hospitals providing women’s health services may need to offer screening of at-risk patients and a broader range of services in order to make sure that the life-saving benefits of mammography are enjoyed on a wider – and more equitable – scale.

A New Breast Imaging Option?

When it comes to mammography screening for women with dense breast tissue, radiologists have long looked for alternatives to established modalities like MRI and ultrasound. In a paper in Radiology: Imaging Cancer, researchers put a new twist on an older technology, positron emission mammography (PEM). 

Molecular imaging technologies like PEM have been investigated for years as potential adjuncts to conventional mammography due to the challenges X-ray imaging has with dense breast tissue. 

  • These technologies have carried different names – PEM, breast-specific gamma imaging, molecular breast imaging – but in the end all have fallen short due to the higher radiation dose they deliver compared to mammography. 

But Canadian startup Radialis has developed a new version of PEM with its Radialis PET Imager that drastically cuts radiation dose by targeting specific organs, enabling clinicians to use far lower doses of radiopharmaceuticals. The company received clearance for the system in 2022. 

  • Radialis touts its system as having high spatial resolution and a small field of view thanks to digital detectors with thousands of silicon sensors that can be placed next to the target organ; this makes it well-suited for imaging specific organs like the breast.

In the new paper, Canadian researchers tested the Radialis system as an adjunct to X-ray mammography in a pilot study of 25 women recently diagnosed with breast cancer. 

  • They wanted to see if PEM performed as well as breast MRI, but with fewer false positives and a radiation dose closer to screening mammography.  

Women underwent PEM at three FDG dose levels – 37, 74, or 185 MBq (for comparison, standard whole-body PET uses 370 MBq, a level that translates to a radiation exposure of 6.2-7.1 mSv). Researchers found …

  • PEM had sensitivity of 87% across all FDG dose levels (MRI was 100%)
    • The sample size was too small to detect statistically significant differences in sensitivity between dose levels
  • PEM had specificity of 95%
  • PEM detected 96% of known index malignant lesions (24 of 25), with the one miss occurring in a patient at the 37MBq level
  • PEM’s radiation dose ranged from 0.62-1.42 mSv, versus 0.44 mSv for a two-view screening digital mammogram

The Takeaway

The findings show that PEM with the Radialis system is a feasible adjunctive breast imaging modality at a radiation dose that’s mostly acceptable relative to X-ray-based mammography. But (as always) additional studies with larger patient populations are needed.

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