Find a breast cancer tumor when it is tiny, and a woman will probably beat the disease. Find that same malignancy when it is larger or has spread to other organs, and she is far more likely to die, even after surgery, radiation and chemotherapy. Finding breast tumors before they turn deadly is a challenge and one that medical technology has so far failed to master.

“We desperately need better breast cancer screening tools,” says Otis Webb Brawley, chief medical officer at the American Cancer Society. His organization promotes mammography in an effort to reduce the 40,000 deaths from breast cancer every year in the U.S. But that emphasis, Brawley fears, leads engineers and medical device manufacturers to presume that the problem of breast cancer detection is not worth their attention, because it has been solved. It has not. Mammograms miss up to 20 percent of tumors, and an average of one out of 10 readings mistakenly identifies healthy breast tissue as possibly malignant. Those false positives mean that women who try to do the right thing by going in for routine cancer screening face a substantial risk of needless biopsies (which can themselves be disfiguring and interfere with treatment later on) and expense, as well as the misplaced fear that they have cancer when they really do not.

Mammography’s shortcomings have spawned controversy and confusion. In 2009 the U.S. Preventive Services Task Force (USPSTF) determined that routine mammograms would save too few lives of women ages 40 to 49 to justify the number of false positives and unnecessary biopsies that would result in that age group. Medical societies and patient advocacy groups attacked the recommendation; the American Cancer Society still advises women in their 40s to undergo mammography every year. Some health experts fret, though, that the USPSTF finding has discouraged more than a few women, not just those in their 40s, from getting tested. “It’s made women more skeptical about the test,” says Sheryl Gabram-Mendola, a surgical oncologist at Emory University’s Winship Cancer Institute. “Women say, ‘I’m just not going to do it, I’m too busy.’”

Even before the 2009 controversy, however, women were forgoing screening mammograms. According to the most recent data from the U.S. Centers for Disease Control and Prevention, the percentage of women who have undergone mammograms within the previous two years has dropped a bit across all age groups. For women 40 to 49, the number fell from 64.3 percent in 2000 to 61.5 percent in 2008—which makes sense if mammograms are unhelpful as screening tests in that age group. For women 50 to 64, it fell from 78.7 percent in 2000 to 74.2 percent in 2008—which is worrisome given that the evidence shows mammograms are clearly beneficial for women 50 and older.

Better tools could help encourage screening and make it more useful for women of all ages. No method currently under study is robust enough yet to supplant mammography. But researchers and clinicians hope that a greater understanding of the physiology and biochemistry of breast cancer, combined with more dexterous technology, will one day result in screening tools that can replace or inexpensively supplement mammograms so that the results will be more trustworthy.

Today’s Options
Mammography, which has been used to detect tumors since the 1970s, misses some cancers and wrongly suggests the presence of others because it is based on low-dose x-rays, which have ­inherent limitations in their ability to resolve tumors. When viewed with x-rays, a malignancy appears lighter in color than does normal breast tissue. X-rays also pick up white specks of calcium deposits that may be generated by a tumor as it grows. But x-rays are not good at spotting tiny tumors, partly because of a lack of contrast and partly because the calcifications associated with tumors are much smaller than benign deposits and therefore easy to overlook. Nor are x-rays good at detecting tumors in dense breast tissue, which also reads as white; many women younger than 50 have dense breasts. Finally, mammograms cannot indicate for sure whether an unusual mass is cancerous.

Two other commonly used imaging techniques—magnetic resonance imaging (MRI) and ultrasound—often supplement mammography to detect breast cancer but are not yet reliable enough to be used by themselves for screening. MRI uses magnetism and radio waves to measure differences in the water content of tissue, which provides more detail about differences in the composition of breast tissue than do x-rays. But because a benign cyst often looks like a tumor on an MRI, screening with MRI also increases the rate of false positives. For that reason, the American Cancer Society recommends annual MRI screenings only in women with a strong family history of breast or ovarian cancer. In addition, breast MRIs are too expensive for routine use in the general population, running $2,000 to $6,000 a test compared with a few hundred dollars for a mammogram.

Ultrasound relies on high-frequency sound waves to characterize the internal structures of the breast. Unlike MRI, it can determine if a lump is a harmless, fluid-filled cyst. But its images cannot distinguish malignant tumors from benign growths filled with harmless breast tissue. It thus gives more false negatives than mammography does, which is why it is less than ideal as a stand-alone method for initial screening.

Fresh Ideas
Researchers, in their quest for better solutions, are experimenting with new twists on an age-old method: feeling for lumps. Tumors are stiffer than healthy breast tissue—which is why they feel different. The problem with waiting until a tumor has grown large enough to be felt, however, is that the delay increases the odds that the cancer will have spread by the time it is diagnosed. The goal is to create ways of detecting that stiffness while a tumor is still too small to be felt by human hands.

One method for measuring such stiffness depends on a combination of low-frequency sound waves and MRI. Dubbed magnetic resonance elastography, the technique was first developed more than a decade ago by Richard Ehman, a radiologist at the Mayo Clinic. Currently applied to the diagnosis of nonmalignant liver diseases, the approach is now being tested on breast tumors. Patients are scanned in an MRI while sound waves with a frequency of 60 hertz pass through plastic tubes to the breasts. The MRI picks up tiny variations in how tissue is moved by the sound waves. Ehman says his team has gotten pretty good at distinguishing between normal and malignant breast tissue based on the stiffness revealed by the MRI. But for elastography to work as a population-wide screening tool, the cost of using an MRI would have to be much lower.

Another technique for measuring tissue stiffness dispenses with the expense and claustrophobia of an MRI. Bruce Tromberg, a biomedical engineering professor at the University of California, Irvine, has built a handheld scanner that sends near-infrared light through the skin and into the breasts and then measures how the light energy scatters on its path through the body before it gets reflected back to the scanner. The light photons travel differently through tumors than through normal tissue. The experimental device is being tested in cancer patients to see whether it can be tuned to accurately measure tumor shrinkage in response to therapy. Tromberg hopes, though, that the technology can eventually be refined enough to spot malignancies while they are still microscopic.

A simpler screen, like a blood test, would be ideal. Physicians do have blood tests that detect the recurrence of breast and ovarian cancer, such as by measuring a molecule called CA125, but they are not accurate enough for large-scale screening. Several researchers, however, are tracking chemical markers in the blood and in the breath with the goal of creating screening tools that could someday not just find cancer but also indicate how dangerous it is likely to be.

Emory’s Gabram-Mendola and chemists at the Georgia Institute of Technology have found markers in the breath of 20 breast cancer patients that were not present in the breath of 20 control subjects. The team is not focusing on fully replacing mammography but on saving it to use as a follow-up tool in places where resources are scarce. “There is a huge need to come up with something that can be used in countries where mammography is less available,” says Charlene Bayer, who is leading the effort at Georgia Tech. A breath test performed in a doctor’s office could also have great appeal for the many women in developed countries who shun screening mammograms because of the discomfort and inconvenience.

Meanwhile developing a single, perfect detection tool for spotting breast cancer remains a tall order. “The technology needs to be able to identify many, preferably most or all, of the people who have the disease,” says David Dershaw, attending radiologist and emeritus director of breast imaging at Memorial Sloan-Kettering Cancer Center in New York City. “It needs to be reasonably noninvasive, tolerable and acceptable to people so they will undergo the test. It needs to be not very expensive. And it has to be widely available.” Nothing under study fits that bill better than mammograms do—at least for now.

Where does that leave women in their 40s? Many doctors who no longer advise mammograms for most women younger than 50 continue to suggest them for those with a family history of breast or ovarian cancer. But for now the majority of women in their 40s will have to continue to struggle with the to-screen-or-not-to-screen question—and a realization that when it comes to tracking down breast cancer, there is still no perfect tool.