MAMMOGRAPHY, THE BOOB-SMOOSHING imaging technique used to detect breast cancer, has an overdiagnosis problem. Doctors have long known that some portion of the tumors revealed by the scans might never become life-threatening—but they haven’t been able to discern harmless growths from those that grow and spread. Finally, though, researchers have learned which cancers account for the majority of problematic diagnoses—and their work suggests mammograms are better at catching innocuous tumors than deadly ones.
In a paper published Wednesday in The New England Journal of Medicine, Yale University scientists analyzed invasive tumor data from hundreds of thousands of breast cancer patients nationwide. The researchers divided the tumors according biological features—how closely they resembled normal breast cells and whether they had certain hormone receptors. Turns out those features could predict whether a small tumor would grow into a big one. Most don’t. And those that do become problematic grow so quickly that mammograms rarely identified them before patients could feel a lump.
“For 100 years we thought that small cancers had a better prognosis because we caught them earlier,” says surgeon and study co-author Donald Lannin. “But it turns out small cancers have better outcomes because they’re fundamentally different in their composition.”
That raises some big questions about the value of early detection and diagnosis. Researchers have spent the past few years calling for a crackdown on breast cancer overdiagnosis. An incorrect diagnosis wastes time and money on treatments that may not help, and causes unnecessary anxiety. At the same time, though, a growing number of health care companies are urging women to seek even earlier preventive care in the form of genetic testing. Those tests provide anything but simple answers—and they too can send frightened patients chasing treatments they may not need, or may not benefit from.
Genetic tests really sell the promise of precision medicine—that more information leads to better healthcare options. But when it comes to breast cancer, those promises are hard to deliver on. The biggest impact lies with treatment, even if that might mean no treatment at all.
In the early 1960s, one of every three women diagnosed with breast cancer died within five years. Over the next few decades, as mammograms emerged as the primary method for detecting early cancerous lesions, those odds improved significantly. The idea that better screening tools led to better outcomes stemmed from a simple, universally accepted truth: Small tumors carry a better prognosis than large ones. The earlier you find the tumor, the smaller it is, and the better chance your chance of survival.
And so science set about making mammography technology ever more sensitive. Over the last 30 years, radiologists have learned to detect cancers as small as 1 millimeter. But doctors didn’t see a commensurate drop in the number of large cancers, or in mortality rates. In the past decade and a half, as genetic tests for some of the genes associated with a high risk of breast cancer (BRCA1/2, TP53, E-Cadherin, and others) became widely available, mortality rates have improved by just 1 percent.
Yet the number of women in the US receiving double mastectomies tripled in the same timeframe. And according to a study published April in the Journal of Clinical Oncology, many of those women didn’t need that procedure. A Stanford University survey of more than 2,000 women who had mastectomies found that half of them didn’t carry the genetic mutations known to increase the risk of additional cancers. Instead, the women had what are known as variants of uncertain significance, ones that often turn out to be harmless.
Granted, genetic testing absolutely helps women with high-risk backgrounds—if their mothers and aunts and grandmothers all had the disease. Such information can help them make informed decisions about a course of treatment. But in the absence of a strong family history, the value of preventive genetic testing is significantly degraded.
Until recently, the prevailing theory among cancer researchers was that most breast cancers have a lead time of three to four years, give or take. (Lead time being the time between when a mammogram can discern a tumor, and when that tumor becomes problematic.) But Lannin’s study showed that most aggressive cancers progress to life-threatening within just a year or two. On the other hand, a large proportion of small cancers grow so slowly that they have a lead time of as long as 20 years. Since breast cancer is most frequently diagnosed among women aged 55 to 64, that means that some patients may never actually get cancer. These women could avoid the expense and side effects of chemotherapy, hormone therapies, and mastectomies, all of which remain blunt instruments of disease control.
This is where precision medicine is only beginning to make its mark: not in diagnosis, but in treatment. In recent years, doctors have increasingly turned to genetic tests to analyze tumors—to see if the cells might respond to hormone therapy. If not, doctors can recommend other treatments, like chemo. It’s just a start, but other assays are in development. And combining these kinds of tests with physical features of the tumor cells can give doctors a much better idea about whether a cancer will become deadly. If it is, patients still need better, more targeted treatments than doctors have now. But for cancers that remain small, doctors and patients may have to get comfortable with the idea of redefining cancer as something you can live with. Because sometimes, the most personalized medicine may be no medicine at all.