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Little progress in how to advise women with dense breasts

Lawmakers around the country are rushing to enact laws that require providers to notify women if their screening mammograms find dense breast tissue. Meanwhile, clinicians remain at a loss concerning how to counsel such women.

As of early August 2015, nearly half the states have laws requiring health professionals to report mammographic breast density to patients. Some also require that the report include information on supplemental screening tests. But although ultrasonography and magnetic resonance imaging (MRI) can detect cancers that mammography missed, many questions remain unanswered, including the effect on morbidity and mortality, cost-effectiveness, and insurance coverage.

The problem is widespread, since up to half of all women reporting for screening mammograms have breasts classified as extremely or heterogeneously dense. The problem is especially common for women in their 40s. Dense breasts (those with a high proportion of fibroglandular, as opposed to fatty, tissue) can hide small cancers. Mammographic density is also an independent risk factor for breast cancer, especially advanced cancer.

For 40 years, researchers have worked to understand and refine that risk, but progress has been slow. In May, Karla Kerlikowske, M.D., of the San Francisco Veterans Affairs Medical Center and the University of California–San Francisco, and colleagues reported the results of a prospective cohort study. They found that not all women with dense breasts are at increased risk—only those with additional risk factors.

Kerlikowske’s group looked at interval cancers—breast cancers diagnosed within a year of a normal mammogram. Interval cancers can be especially aggressive, so adjunct screening tests would probably be most beneficial in women at high risk for such cancers.

The team analyzed more than 800,000 digital screening mammograms from 365,426 women. They calculated each woman’s five-year risk of developing breast cancer by using the Breast Cancer Surveillance Consortium risk model. That tool factors in age, first-degree relatives with breast cancer, biopsy history, race or ethnicity, and density on BI-RADS (the Breast Imaging Reporting and Data System).

The researchers defined a high rate of interval cancers as more than one case per 1,000 mammograms. Women with extremely dense breasts had high rates if they also had a five-year breast cancer risk of 1.67% or greater, as did women with heterogeneously dense breasts with a five-year risk of 2.5% or higher. That added up to 24% of those with dense breasts.

State notification laws “say you should inform women if they have dense breasts and advise them about supplemental imaging,” Kerlikowske said. “But you can’t perform supplemental screening on all women with dense breasts—which is 27 million in the U.S. You should target those discussions to the 24% who are really at high risk.”

Kerlikowske pointed out that the women in her high-risk group were at risk not only of missed cancers but also of advanced cancers. “If you’re going to do supplemental screening,” she said, “that would be the group.”

The Kerlikowske study offers “compelling evidence that breast density should not be the sole criterion to guide decisions about supplemental breast cancer screening,” wrote Nancy Dolan, M.D., and Mita Sanghavi Goel, M.D., both of Northwestern University in Chicago, in an accompanying editorial.

More than 43% of women aged 40–74 years have dense breast tissue, according to a study published last year. Other studies put the proportion of women with dense breasts closer to 50%. And that number could rise with the implementation of a new BI-RADS system. Instead of assessing the percent area of a mammogram that contains dense tissue, the new system classifies any breast with a particularly opaque area as a dense breast, and the classification applies to the denser breast.

Edward Sickles, M.D., professor emeritus and former chief of breast imaging at UCSF, said this reflects that the more serious problem of mammographic density is its ability to mask cancers, rather than its effect on breast cancer risk.

“Although breast cancer risk is slightly higher in women with dense breasts,” Sickles said, “the increased risk has been exaggerated in some publications, which compared those with the densest breasts to those with the fattiest breasts. If you compare a woman with heterogeneously dense breasts to the average woman, her risk is only 1.2 times higher—a rather low level of risk that doesn’t support supplemental screening.” Even women with extremely dense breasts are only 2.1 times more likely than women with average density to develop breast cancer—a risk equivalent to having a first-degree relative with the disease.

Grassroots advocates have persuaded lawmakers in 24 states so far—including New York, Texas, and California—to mandate that providers notify women whose breasts were found to be dense on mammography. Some laws add that women should be urged to discuss supplemental screening tests with their doctors. Similar federal legislation is also pending. However, experts have expressed concern that such notice can create anxiety in patients—and confusion among physicians—because it’s unclear how women with dense breasts can reduce their risk.

“There’s a lot of variability in what’s being reported back to women,” said Rulla Tamimi, Sc.D., a researcher at Harvard Medical School, Brigham and Women’s Hospital, in Boston. “Those laws happened before we were ready. We don’t have clear guidelines or recommendations for these women or their physicians. There’s still so much we don’t know.”

The Texas and Louisiana statutes, for example, require mammographers to give the following notice to patients: “If your mammogram demonstrates that you have dense breast tissue, which could hide abnormalities, and you have other risk factors for breast cancer that have been identified, you might benefit from supplemental screening tests that may be suggested by your ordering physician.” Connecticut, the first state to pass a density notification statue, requires physicians to offer supplemental ultrasonography, MRI, or both to all women with dense breasts. Unlike most states, Connecticut also requires insurance to cover the additional screening.

Radiology studies have shown that supplemental imaging with ultrasound can detect some cancers that mammography misses in women with dense breasts. However, Brian Sprague, Ph.D., of the University of Vermont Cancer Center in Burlington, and colleagues recently concluded a comparative modeling study. They found that supplemental ultrasonography for these women has little effect on outcome but dramatically increases costs and harms, including a high rate of false positives. (The study, published in January in Annals of Internal Medicine, examined all women with dense breasts without trying to stratify them by risk.) Sprague’s team had looked at ultrasonography because it’s widely available in the clinic and relatively inexpensive. Potential alternatives include fast MRI and digital breast tomosynthesis (DBT), or 3-D mammography. A computer simulation published in March found that adding tomosynthesis to biennial mammography would avert 0.5 deaths and 405 false-positive results per 1,000 women. The additional cost per quality-adjusted life-year saved was $53,893 with tomosynthesis, compared with $325,000 with ultrasonography in the Sprague study.

But “DBT is not going to be a supplement for 2-D mammography,” said Daniel Kopans, M.D., the Harvard radiology professor who invented DBT. “It will completely replace 2-D mammography, just as digital mammography has replaced screen-film mammography. . . . DBT is actually a much better mammogram, since it finds many more early cancers while having fewer recalls.”

A version of this blog post first appeared in Journal of the National Cancer Institute. 

Image credit: “Metastatic Breast Cancer in Pleural Fluid” by Ed Uthman. CC BY 2.0 via Flickr

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