Mammography can prevent deaths from breast cancer, but it's not a perfect test.

It misses some cancers, especially in women with dense breast tissue, and flags abnormalities for follow-up tests that turn out to be benign, among other issues. So there's a lot of interest in additional tests that might make screening more accurate in women who have dense breasts.

Many of those women may be wondering about extra screening after receiving notification letters saying that their mammogram was clean, but that their dense breasts put them at higher risk of cancer.

But there is no clear path for those women, who make up about 45 percent of women ages 40 to 74. The goal with breast imaging technology is not only to detect more cancers earlier, but to actually prevent deaths from breast cancer, says Dr. Otis Brawley, chief medical officer for the American Cancer Society. "That's a very separate and different question," he says. And so far, only mammography has met that standard, he says.

Investigating that question requires large, randomized clinical trials that follow women for many years to track whether the group screened with the extra technology has fewer deaths from breast cancer than the group screened with mammography alone. And that kind of trial is expensive and logistically tough.

Because cancer isn't as common as many people think, "the number of women you have to screen to achieve statistical significance is huge," says Barbara Monsees, a professor of radiology and women's health at the Washington University School of Medicine in St. Louis. The full effects won't be apparent for decades. "It's a long-term commitment, and it costs a lot of money," she says.

So researcher, clinicians and policymakers who evaluate tests have to rely on studies of shorter-term outcomes like cancer detection rates and stage at detection — which may or may not translate to saved lives. They also look at what those studies say about false positive findings, since those can lead to invasive biopsies to see if cancer is actually present.

The New England Comparative Effectiveness Public Advisory Council, whose members are from the fields of medicine, economics and policy, looked at the evidence supporting any kind of supplementary screening in women with dense breasts and a clear digital mammogram. Their conclusions, published in 2014, found that there's not a ton of evidence on long-term outcomes, but that the available research suggests a net benefit depending on a person's underlying cancer risk from additional factors, namely age and family history of the disease.

For otherwise low-risk women with dense breasts, the New England group determined that there wasn't enough evidence to recommend extra screening. They mentioned the potential of overdiagnosis and overtreatment, since some percentage of breast cancers — and there is much controversy over how many — would likely never have caused a woman harm had they been left undiscovered.

But for women with dense breasts who are at moderate or high risk of breast cancer according to family history and age, they voted that from the available evidence, the benefits of routine supplemental screening are more likely to outweigh the harms.

If a woman and her doctor decide that supplemental screening is needed because of her risk factors, the next question is what kind of screening. There are pluses and minuses of each technology:

Hand-held ultrasound devices use sound waves to visualize breast tissue. Ultrasound is often used in women with dense breasts. And research suggests that it can pick up more cancers in these women, ones missed by mammograms. "But there's a price for that," says Debra Monticciolo, chair of the American College of Radiology's Commission on Breast Imaging and a professor of radiology at Texas A&M University College of Medicine. There are many, many more false positives, she says, which in turn can lead to unneeded biopsies.

And it's unclear how those benefits and harms balance out. "Does finding those cancers impact long-term outcomes? You can't really prove it, because all you know is that you found additional cancers," says Monsees. "Can you guess if those would translate into saved lives? Perhaps not all of them, but what percentage of them?"

Magnetic resonance imaging, or MRI, uses magnetic waves to produce images of the breast. MRI finds more cancers, but it also leads to more false positive results than mammography, although fewer than ultrasound. It requires an intravenous catheter for the contrast agent used in the test, and is more expensive than ultrasound.

Most of the members of the New England group said MRI was their first choice for women with dense breasts and a high risk of cancer, citing research on its utility among high-risk women in general. And despite the lack of direct evidence that it saves lives, the American Cancer Society recommends it be added to mammography for women at very high risk of breast cancer, including women who carry certain genetic mutations. That group says there's not enough evidence to say whether women who are moderate risk or who have dense breasts should get the test, and it recommends against its use in low-risk women.

Tomosynthesis is basically a souped-up mammogram; it uses the same X-rays to generate multiple images. It's sometimes called a 3-D mammogram. And unlike the other technologies, it's being suggested for use in all women, says Dr. Janie Lee, associate professor of radiology at the University of Washington and director of breast imaging at the Seattle Cancer Care Alliance. (Lee was one of the authors of the New England group's technology assessment but not a voting member.) It can be used along with a separate 2-D digital mammogram or a virtual 2-D image digital mammogram image can be derived from the 3-D one. (Using the latter technique keeps the radiation dose comparable to a standard digital mammogram.)

Studies suggest that tomosynthesis may improve the cancer detection rate, lower the proportion of women who are called back for follow-up tests, or both, says Monsees, which makes it attractive when performed with the method that produces the lower radiation dose. But it likely won't significantly improve the callback rate in experienced radiologists who already have low recall rates, says Brawley.

Molecular breast imaging involves injecting a radioactive tracer that circulates through the body and is attracted to cancer. Research suggests that it can pick up more tumors in women with dense breasts, and it's cheaper than MRI. But the doses of radiation administered are generally larger than with mammography, notes Monticciolo. And while mammography exposes just the breast to radiation, MBI exposes other organs such as the GI tract. That means that at this point, says Lee, it's more of a candidate for head-to-head studies against MRI for women with dense breasts who are also at high risk of the disease because of other factors.

Researchers are pushing ahead to see if screening methods can be more tailored to an individual woman's risk. So far, though, there's no proven ideal option — which means the best course of action is to know your risk, and talk to your physician about your options.

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