What the Dog Saw

“The body has this whole mechanism to repair things, and maybe that’s what happened with these tumors.” Gilbert Welch, the medical-outcomes expert, thinks that we fail to understand the hit-or-miss nature of cancerous growth, and assume it to be a process that, in the absence of intervention, will eventually kill us. “A pathologist from the International Agency for Research on Cancer once told me that the biggest mistake we ever made was attaching the word ‘carcinoma’ to DCIS,” Welch says. “The minute carcinoma got linked to it, it all of a sudden drove doctors to recommend therapy, because what was implied was that this was a lesion that would inexorably progress to invasive cancer. But we know that that’s not always the case.”

In some percentage of cases, however, DCIS does progress to something more serious. Some studies suggest that this happens very infrequently. Others suggest that it happens frequently enough to be of major concern. There is no definitive answer, and it’s all but impossible to tell, simply by looking at a mammogram, whether a given DCIS tumor is among those lesions that will grow out from the duct, or part of the majority that will never amount to anything. That’s why some doctors feel that we have no choice but to treat every DCIS as life-threatening, and in 30 percent of cases that means a mastectomy, and in another 35 percent it means a lumpectomy and radiation. Would taking a better picture solve the problem? Not really, because the problem is that we don’t know for sure what we’re seeing, and as pictures have become better we have put ourselves in a position where we see more and more things that we don’t know how to interpret. When it comes to DCIS, the mammogram delivers information without true understanding. “Almost half a million women have been diagnosed and treated for DCIS since the early nineteen-eighties—a diagnosis virtually unknown before then,” Welch writes in his new book, Should I Be Tested for Cancer?, a brilliant account of the statistical and medical uncertainties surrounding cancer screening. “This increase is the direct result of looking harder—in this case with ‘better’ mammography equipment. But I think you can see why it is a diagnosis that some women might reasonably prefer not to know about.”

6.

The disturbing thing about DCIS, of course, is that our approach to this tumor seems like a textbook example of how the battle against cancer is supposed to work. Use a powerful camera. Take a detailed picture. Spot the tumor as early as possible. Treat it immediately and aggressively. The campaign to promote regular mammograms has used this early-detection argument with great success because it makes intuitive sense. The danger posed by a tumor is represented visually. Large is bad; small is better—less likely to have metastasized. But here, too, tumors defy our visual intuitions.

According to Donald Berry, who is the chairman of the Department of Biostatistics and Applied Mathematics at M. D. Anderson Cancer Center, in Houston, a woman’s risk of death increases only by about 10 percent for every additional centimeter in tumor length. “Suppose there is a tumor size above which the tumor is lethal, and below which it’s not,” Berry says. “The problem is that the threshold varies. When we find a tumor, we don’t know whether it has metastasized already. And we don’t know whether it’s tumor size that drives the metastatic process or whether all you need is a few million cells to start sloughing off to other parts of the body. We do observe that it’s worse to have a bigger tumor. But not amazingly worse. The relationship is not as great as you’d think.”

In a recent genetic analysis of breast-cancer tumors, scientists selected women with breast cancer who had been followed for many years, and divided them into two groups—those whose cancer had gone into remission, and those whose cancer had spread to the rest of their body. Then the scientists went back to the earliest moment that each cancer became apparent and analyzed thousands of genes in order to determine whether it was possible to predict, at that moment, who was going to do well and who wasn’t. Early detection presumes that it isn’t possible to make that prediction: a tumor is removed before it becomes truly dangerous. But scientists discovered that even with tumors in the one-centimeter range—the range in which cancer is first picked up by a mammogram—the fate of the cancer seems already to have been set. “What we found is that there is biology that you can glean from the tumor, at the time you take it out, that is strongly predictive of whether or not it will go on to metastasize,” Stephen Friend, a member of the gene-expression team at Merck, says. “We like to think of a small tumor as an innocent. The reality is that in that innocent lump are a lot of behaviors that spell a potential poor or good prognosis.”

The good news here is that it might eventually be possible to screen breast cancers on a genetic level, using other kinds of tests—even blood tests—to look for the biological traces of those genes. This might also help with the chronic problem of overtreatment in breast cancer. If we can single out that small percentage of women whose tumors will metastasize, we can spare the rest the usual regimen of surgery, radiation, and chemotherapy. Gene-signature research is one of a number of reasons that many scientists are optimistic about the fight against breast cancer. But it is an advance that has nothing to do with taking more pictures, or taking better pictures. It has to do with going beyond the picture.

Under the circumstances, it is not hard to understand why mammography draws so much controversy. The picture promises certainty, and it cannot deliver on that promise. Even after forty years of research, there remains widespread disagreement over how much benefit women in the critical fifty-to-sixty-nine age bracket receive from breast X-rays, and further disagreement about whether there is enough evidence to justify regular mammography in women under fifty and over seventy. Is there any way to resolve the disagreement? Donald Berry says that there probably isn’t—that a clinical trial that could definitively answer the question of mammography’s precise benefits would have to be so large (involving more than five hundred thousand women) and so expensive (costing billions of dollars) as to be impractical. The resulting confusion has turned radiologists who do mammograms into one of the chief targets of malpractice litigation. “The problem is that mammographers—radiology groups—do hundreds of thousands of these mammograms, giving women the illusion that these things work and they are good, and if a lump is found and in most cases if it is found early, they tell women they have the probability of a higher survival rate,” says E. Clay Parker, a Florida plaintiff’s attorney, who recently won a $5.1 million judgment against an Orlando radiologist. “But then, when it comes to defending themselves, they tell you that the reality is that it doesn’t make a difference when you find it. So you scratch your head and say, ‘Well, why do you do mammography, then?’”

The answer is that mammograms do not have to be infallible to save lives. A modest estimate of mammography’s benefit is that it reduces the risk of dying from breast cancer by about 10 percent—which works out, for the average woman in her fifties, to be about three extra days of life, or, to put it another way, a health benefit on a par with wearing a helmet on a ten-hour bicycle trip. That is not a trivial benefit. Multiplied across the millions of adult women in the United States, it amounts to thousands of lives saved every year, and, in combination with a medical regimen that includes radiation, surgery, and new and promising drugs, it has helped brighten the prognosis for women with breast cancer. Mammography isn’t as good as we’d like it to be. But we are still better off than we would be without it.

“There is increasingly an understanding among those of us who do this a lot that our efforts to sell mammography may have been overvigorous,” Dershaw said, “and that although we didn’t intend to, the perception may have been that mammography accomplishes even more than it does.” He was looking, as he spoke, at the mammogram of the woman whose tumor would have been invisible had it been a few centimeters to the right. Did looking at an X-ray like that make him nervous? Dershaw shook his head. “You have to respect the limitations of the technology,” he said. “My job with the mammogram isn’t to find what I can’t find with a mammogram. It’s to find what I can find with a mammogram. If I’m not going to accept that, then I shouldn’t be reading mammograms.”

7.

In February of 2002, just before the start of the Iraq war, Secretary of State Colin Powell went before the United Nations to declare that Iraq was in defiance of international law. He presented transcripts of telephone conversations between senior Iraqi military officials, purportedly discussing attempts to conceal weapons of mass