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Millions of American women over age 40 receive regular mammograms to screen for breast cancer. About half of them turn out to have dense breast tissue — which makes screening significantly more complicated.

“It’s kind of a double whammy because dense breast tissue not only makes cancers harder to find, but people with denser tissue are more likely to get breast cancer,” said Laurie Margolies, a radiologist and vice chair for breast imaging at Mount Sinai in New York. (While people with dense breast tissue are at higher risk of breast cancer, their mortality risk is not higher than people with non-dense breasts, according to the Centers for Disease Control and Prevention.)

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Dense breast tissue means that people have more fibrous and glandular tissue, which appears white on a mammogram, than fatty tissue. Cancer, too, looks like a white mass on a mammogram, so dense breasts can make it harder to detect. A mammogram will miss cancer in dense breasts in almost half of such cases.

But while it’s well known that dense breast tissue can make mammograms less effective, there’s not yet a clear protocol about how to handle this common issue. So far, 38 states have laws requiring that people identified as having dense breast tissue receive a letter informing them of it, and recommending they contact their providers, who can discuss potential follow-ups and risk assessment. New Food and Drug Administration guidelines made this a federal policy in 2023, and facilities have until September 2024 to implement it.

Even when people are informed that they have dense breast tissue, the onus is typically on the patient to seek further advice from their referring physician — who may not be especially experienced in screening options.

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“People in the breast imaging world and the breast surgery world, we all know about it. But the primary care providers, the gynecologists and the internists, some are very well versed in it and others may not be as comfortable having a nuanced discussion about the benefits of having supplemental screening,” said Margolies.

That’s a problem because many experts believe people with dense breast tissue do need additional tests, JoAnn Pushkin, the executive director of educational nonprofit DenseBreast-info, wrote in an email to STAT.

“A mammogram alone for a woman with dense breasts is incomplete screening,” she said. But there is no consensus on the best additional screening tool, and the current available options offer different pros and cons.

From breast ultrasounds to abMRIs

Dense breast tissue is normal. People can have it for a number of reasons, including genetics, age (breast tissue tends to get less dense over time, and especially after menopause), and breast size (smaller breasts are often more dense). The only way to identify it is through a mammogram.

After that point, practices must independently evaluate and recommend one screening or the other. “We have some options, but none of them are clear-cut because there’s no guidelines from any major society about what the next best step is,” said Kelly Myers, an assistant professor in the department of radiology at Johns Hopkins University.

The American College of Radiology (ACR), for example, has specific guidelines for cases when the lifetime risk of breast cancer is 20% or greater, compared to a baseline of 12% for any woman. But having dense breast tissue alone doesn’t clear this benchmark in the absence of other compounding risk factors, such as BRCA gene mutations, or direct family history of breast cancer.

“The ACR periodically updates its guidelines and its appropriateness criteria as evidence dictates,” Shawn Farley, a spokesperson for the ACR, wrote in an email to STAT. Farley said the organization may update its supplemental screening guidance in coming months.

The most common follow-up after a mammogram detects dense breast tissue is a breast ultrasound, said Myers, noting that dozens of studies have shown that breast ultrasounds identify up to 50% more cancers in patients with dense breast tissue compared to a regular mammogram. It is a low-risk, easily available exam, and one that is often covered by insurance.

The downside: Breast ultrasounds have a higher than 90% rate of false positives, recommending patients for biopsies that ultimately find benign cells. That comes with financial and psychological costs. “Because of all those false alarms, even though we find 50% more cancers than mammograms alone [do] in women with dense breasts … it just remains an optional test that I think is very individual for the patient,” said Myers.

Another option is a full-protocol MRI — an exam that can identify up to 200% more cancers in women with dense breast tissue compared to mammograms. This is the standard of care for those who have a 20% or greater lifetime risk of breast cancer, and “it is absolutely the single, most sensitive, best tool we have for detecting breast cancer,” said Myers.

However, MRIs are long, costly exams that may not even be available within driving distance for some people. And recently, research has shown that with repeated dosage (which would be required to perform repeated screening MRIs on women with dense breasts), gadolinium — the contrast agent used in them — can deposit in certain body tissues, including in the brain. This hasn’t been shown to lead to specific problems, but is still a potential concern that may limit the frequency with which it is prescribed.

In hopes of addressing the costs of MRIs, in the past few years doctors have been studying a shorter, simpler version known as abbreviated breast MRI, or abMRI. While a full-protocol MRI takes a half hour, an abMRI only takes less than ten minutes and is limited to taking only the most high-priority set of images.

Studies have shown that abMRIs are very effective in identifying otherwise overlooked cancers, and have a lower false positive rate (70-80%) than ultrasounds (90%). But they have their own set of logistical and financial issues, Myers explained. First, most centers schedule MRIs in 30-minute increments, and would lose precious machine time if they only had 10 minutes allocated for a certain slot. Another problem: “There’s essentially no way to bill for an abbreviated MRI, so there’s no way for insurance to reimburse for it,” Myers said. In the few centers that offer abMRIs, it’s typically a cash service, ranging between $300 and $500.

One last option, Myers said, is a contrast-enhanced mammogram, done with a contrast fluid that’s different from the one used in the MRI. This has shown very good cancer detection rates, but only in very small studies of up to 900 people.

“I think there’s just not currently enough of a consensus to say which is the best screening methodology. We just know that these all pick up additional cancers in these women who benefit slightly less from mammography than the typical woman with non-dense breasts,” said Laura Heacock, an associate professor of radiology and breast imaging specialist at NYU Langone Perlmutter Cancer Center.

The cost of follow-up screenings

Not everyone believes the current available evidence suggests women with dense breast tissue need increased follow-up screening.

“At this point, for women who are at average risk, I’m not generally recommending whole breast ultrasound or breast MRI for women with dense breasts. Instead, I’m recommending an annual mammography with tomosynthesis, or a 3D mammography,” said Nancy Lynn Keating, a professor of health care policy and medicine at Harvard Medical School. 3D mammograms have been shown to be better at identifying cancer despite dense breast tissue than 2D technology.

Keating acknowledges that mammograms have limitations and that better strategies are needed. But based on the current evidence, Keating believes additional screenings — which have not so far been associated with significantly lower mortality in women who aren’t high-risk — may do more harm than good.

For this reason, she said, insurance coverage of follow-up screenings for all women with dense breasts is not justified.

“We just don’t have enough evidence to support that our health care dollars should be spent this way, because we’re spending them on unproven tests that are likely to have more harm than benefit,” she said.

While the majority of other experts who spoke with STAT were in favor of additional screenings, they noted that insurance coverage will be a significant hurdle.

“The challenge always is getting reimbursement. You know, just because of the notification law, many women will get this letter saying they have dense breasts and they need supplemental screening, but their insurance may not cover this supplemental screening,” said Heacock. “So the notification law doesn’t guarantee insurance coverage — that’s on a state by state basis and on a plan by plan basis.”

In order to make supplemental screenings more accessible, DenseBreast-info worked with Reps. Rosa DeLauro (D-Conn.) and Brian Fitzpatrick (R-Penn.) on the draft and introduction of the federal Find It Early Act, Pushkin said. “The bill would ensure all health insurance plans cover screening and diagnostic breast imaging with no out-of-pocket costs for women with dense breasts or at higher risk for breast cancer and close loopholes inherent in individual state laws,” said Pushkin.

Expanding coverage to include follow-up screening tests would hopefully increase the number of people with breast cancer who get diagnosed. Experts also noted that studies may soon offer more information about exactly which tests it would be most effective for insurers to cover.

“This is a very active research topic,” Myers said, “and so I think we’re going to learn a lot more in the next few years.”

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