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While major guidelines support mammography for routine breast cancer screening in average-risk women, the decision to offer additional screening and which supplemental tool to use can become more complicated.

Certain supplemental screening options improve cancer detection but may increase the risk for false-positive findings and unnecessary biopsies, while others may offer limited additional cancer detection benefits.

Ultimately, "not all supplemental screening tests are created equal," Bethany L. Niell, MD, PhD, a diagnostic radiologist and section chief of breast imaging at Moffitt Cancer Center, Tampa, Florida, told Medscape Medical News. At the recent National Comprehensive Cancer Network (NCCN) annual conference, Niell explored differences among some of the most common supplemental modalities — including digital breast tomosynthesis, ultrasound, and MRI — and aimed to help clarify options for different patients.

The decision to undergo supplemental screening and the choice of approach depend on a woman's risk level as well as their specific risk factors, which can include a family history of breast cancer, breast density, and certain genetic mutations.

Overall, women with a lifetime risk under 15% are considered average risk, while those with a lifetime risk over 20% are deemed high risk, with certain factors weighing heavily on that risk assessment. For instance, the lifetime breast cancer risk rises to 72% among BRCA1 carriers and 69% among BRCA2 carriers.

Understanding which women face a higher risk for breast cancer, when to provide additional screening alongside mammography, and what screening approach is likely best in each scenario can improve detection and minimize the likelihood of overdiagnosis.

Comparing Approaches

In 2021, the American College of Radiology (ACR) developed "appropriateness criteria" for supplemental breast screening.

The expert panel outlined that average- or intermediate-risk women with non-dense breasts could receive supplemental screening with digital breast tomosynthesis, also known as three-dimensional mammography, while higher-risk women with non-dense breasts could undergo digital breast tomosynthesis or MRI without and with intravenous (IV) contrast.

For average- or intermediate-risk women with dense breasts, digital breast tomosynthesis is "usually appropriate," but mammography with IV contrast and MRI or abbreviated MRI without and with IV contrast and ultrasound may also be appropriate.

High-risk women with dense breasts have a wider range of appropriate options — digital breast tomosynthesis along with MRI or abbreviated MRI without and with IV contrast and ultrasound.

Although the cancer detection rates associated with these supplemental screening approaches depend on a patient's risk level and breast density, the benefit of detecting more cancers needs to be weighed against the drawback of introducing more false-positive findings and increasing the risk for overdiagnosis.

Research on digital breast tomosynthesis, which captures a quasi-3D image of the breast and displays breast tissue in thin, cross-sectional slices, indicates that this approach can detect more cancers compared with standard mammography alone and reduce false positives.

Overall, studies show that adding digital breast tomosynthesis to mammography increases the rate of cancer detection vs mammography alone by one to three cancers per 1000 women screened, with the greatest improvement observed in women with dense breasts, according to the ACR expert panel.

As for false positives, a 2018 study found that adding digital breast tomosynthesis to mammography decreased the false-positive findings by 15.5 per 1000 women screened.

"Digital breast tomosynthesis has really helped us cut down on those false positives, so this means that [the physician] is less likely to have to recall a patient for a screening mammogram for a finding that is not cancer," Niell explained in her NCCN recent talk.

Ultrasound has the advantage of detecting more cancers than mammography or digital breast tomosynthesis but does come with a higher rate of false-positive and benign biopsies.

A 2020 review of 21 studies reported a pooled sensitivity rate for mammography plus ultrasound in women with dense breasts of 96% vs 74% for mammography alone, but lower specificity rates — 87% vs 93% — which corresponds to almost two times the false-positive rate compared with mammography alone — 13% vs 7%. 

Overall, breast MRI with and without the contrast agent gadolinium significantly increases cancer detection over other screening approaches.

MRI is also associated with nearly no risk for interval cancers between screenings — cancers often linked to worse outcomes — and its accuracy does not depend on breast density, Niell explained.

In fact, studies show that MRI is the best supplemental screening option for average- or intermediate-risk women with dense breasts who had a negative mammogram, with pooled data from 22 studies showing an incremental cancer detection rate of 1.54 cancers per 1000 screenings. That incremental cancer detection rate beat out rates for handheld ultrasound (0.35 per 1000 screenings), automated breast ultrasound (0.26 per 1000 screenings), and digital breast tomosynthesis (0.14 per 1000 screenings).

Abbreviated MRI, which requires fewer sequences and significantly less time, also has demonstrated high accuracy, with research showing a sensitivity of 95.7% for invasive cancer and ductal carcinoma in situ compared with 39% using digital breast tomosynthesis. While its specificity is lower than that seen with digital breast tomosynthesis (87% vs 97%, respectively), abbreviated MRI has a high rate of invasive cancer detection of 12 cancers per 1000 screens, with 96% of detected cancers being node-negative.

An advantage of abbreviated MRI over standard MRI is the appointment time. Standard MRI might take an hour, while the abbreviated scan typically takes about 10 minutes or less, "so the exam is easier to complete for some patients who might have difficulty lying still inside the scanner," Niell said.

Overall, though, MRI — either the standard or abbreviated approach — provides superior detection of breast cancers in most scenarios.

"To my knowledge, there's no group of individuals studied in which MRI does not outperform mammography, digital breast tomosynthesis, or ultrasound," Niell said.

However, MRI does come with some caveats. While MRI has a very high sensitivity for invasive cancers and ductal carcinoma, data show the false-positive rate is higher compared with mammography. Overall, about 1 in 10 screenings with MRI are abnormal,  and the false-positive rate ranges from about 5% to 11%.

"These are helpful numbers to share with your patients to give them realistic expectations," Niell said. "We find a lot more cancers, but we do have to do more biopsies."

And although ultrasound and MRI screening can detect more cancers, not all experts agree on their use for supplemental screening in women with dense breasts.

In the latest update to its breast screening guidelines, for instance, the US Preventive Services Task Force (USPSTF) found "insufficient evidence on the benefits and harms" of supplemental screening with breast ultrasound or MRI in women with dense breasts who had a negative screening mammogram.

The USPSTF's updated recommendations, published on April 30 in JAMA, highlighted that women who underwent supplemental MRI screening experienced additional recalls (94.9 per 1000 screened), false-positive recalls (80.0 per 1000 screened), and false-positive biopsies (62.7 per 1000 screened).

However, in an editorial accompanying the USPSTF guidelines, Wendie A. Berg, MD, PhD, a radiologist at the University of Pittsburgh, Pittsburgh, had a different take. Berg explained that the USPSTF task force "understated" the benefits of supplemental biennial MRI for reducing the incidence of interval cancers because its estimates included women who were invited but declined MRI screening.

When focusing only on women who received biennial MRI screening, just 0.8 of 1000 women screened experienced an interval cancer compared with 4.9 of 1000 who declined the MRI and 5 of 1000 who were not invited, Berg explained.

Regarding the false-positive issue, Berg noted that the rates of false-positive findings decreased significantly between the first year of supplemental MRI to the second.

In another editorial accompanying the USPSTF guidelines, Joann G. Elmore, MD, MPH, of University of California, Los Angeles, and Christoph I. Lee, MD, MS, of the University of Washington, Seattle, agreed that "MRI is the supplement of choice at this time" for women meeting high-risk criteria for supplemental breast screening. The experts added that contrast-enhanced mammography shows promise in this population as well, and screening ultrasonography "can be considered" for those who cannot tolerate or access MRI or contrast-enhanced mammography.

More Screening Tips

Experts highlighted several other key recommendations for clinicians:

• Do not rely solely on family history to estimate risk. "The misconception is that women with no family history or risk factors have no risk," said Andrea V. Barrio, MD, of Memorial Sloan Kettering Cancer Center in New York City, who moderated the NCCN talk. The most common reason for looking at family history is it may indicate the presence of a genetic mutation, added Barrio. Niell agreed, noting that "healthcare providers tend to over rely upon family history and underuse validated breast cancer risk models to estimate breast cancer risk."
• Do not assume every patient is at average risk. Use validated risk models, which are available online, to estimate risk in patients with or without a family history of breast cancer. Validated models vary, but "it is important to use these existing models to predict breast cancer risk rather than focus solely upon the patient's family history of breast cancer or the patient's breast tissue density on the most recent mammogram," Niell said.
• The available evidence also indicates that the best detection rates occur with approaches that include contrast materials compared with those that don't. Screening tests that use injections of contrast material "detect more breast cancers than screening tests that do not use intravenous contrast injections," Niell said.

Niell noted, however, that supplemental screening should not replace screening mammography in most patients.

If a patient is traveling a long distance, Niell will perform a mammogram and a breast MRI, for instance, in 1 day, given the low uptake of mammography in the United States and the even lower rates of breast MRI among high-risk women.

"In an ideal world, the most efficient timing regimen would be to space them — mammogram and MRI, for instance — at 6-month intervals, allowing for each once a year," Niell said.

Niell received research funding from the NIH and NCI. She serves as vice chair of the NCCN Guidelines Panel for Breast Cancer Screening and Diagnosis and is chair of the American College of Radiology Breast Imaging Commission government relations committee. Barrio had no disclosures to report.