More on mammography: just because you don't like the results doesn't make research junk science

A recent study published in the New England Journal of Medicine, “Effect of three decades of screening mammography on breast-cancer incidence”, by Archie Bleyer and H. Gilbert Welch[1], has generated enormous controversy. This has been caused by a combination of the study’s findings, the interpretation of them by the popular press, and the reactions of those who have a vested interest in the status quo – a combination that regularly occurs any time anyone publishes any research questioning the current conduct of screening or treatment for breast cancer (see, for example, my blog post Breast cancer screening: conflicting evidence? what are the important questions for health?, October 30, 2010). It happens in other areas, also, but breast cancer is the most common and in some sense most personal of cancers for women, and has a huge advocacy community, as well as powerful groups who profit from both treating it and screening for it.

What did the study show, what does it mean to people, what is the implication for cancer screening and most important, for the health of people (overwhelmingly women) who might get breast cancer? Before addressing these questions, I think it might be helpful to review a little about screening tests, cancer, and people’s hopes and beliefs. People want to not get sick, and especially don’t want to get cancer. If they do get it, they want to be treated and get all better. Of course, despite the use of “cancer” as if it were a single disease, and the existence of organizations such as the American Cancer Society, the federal National Cancer Institute, and the many Cancer Institutes, hospitals, and specialists, it is in fact a variety of diseases that all share certain characteristics but differ in many others. These include commonness, severity, cause, and likelihood of progression or death with or without treatment. Known causes for some cancers include smoking, radiation and viruses, and for many (including most breast cancer) the cause is unknown. It is even more complicated, because just naming the organ affected (breast, lung colon) is not all there is to it, as there are different kinds of cancer that affect the same organ. Whew. This is why the idea of “a cure for cancer” is unlikely; there are cures for some, and may be cures for others in the future, but there is unlikely to be “a” cure.

Some cancers, like breast cancer, are common enough, and well-publicized enough, that women realize that there is a real risk. In that case, the hope is that there exists a screening test that can identify it early enough to intervene and make a positive difference in the outcome. The first thing is that screening tests, by definition, are only for people who have no symptoms of a disease; once they do, a test, even if it is the same test, is no longer “screening” because the probability of the disease is greater in people with a symptom. For example, if one has a lump in the breast, a mammogram may be a good diagnostic test, but it is no longer a screening test. In looking at the criteria for a good screening test, there must be:

1)      A disease a test can screen for (while this seems obvious, doctors still do tests in asymptomatic people that do not effectively screen for any disease),
2)      A reasonable sensitivity and specificity to the test (meaning people with disease are more likely to have a positive test and those without the disease to have a negative test),
3)      A test that is reasonably cheap and acceptable to patients (tests like mammography and colonoscopy, for example, are both more expensive and more uncomfortable than, say, a blood test),
4)      A more definitive test available to say more definitely whether people who screen positive actually have the disease (for most screening, although those who screen positive are more likely to have the disease than those who do not, the majority of those who screen positive still may not have the disease),
5)      An intervention that can be done in the asymptomatic stage that will prevent the disease from progressing (or else, why not wait until it is symptomatic?)

So how does mammography stack up? This is a big part of what is addressed by the Bleyer and Welch study. They have looked at 30 years of screening in the US and found that screening mammograms have uncovered a large number of early-stage breast cancers; in fact, over that time, the number of early-stage breast cancers identified has doubled (from 112 to 234 cases per 100,000 women per year). This is a good – particularly if criterion #5, above, is met – and they can be treated and prevent women from dying or suffering serious morbidity. If this is happening, then (assuming the actual rate of cancer stays the same) the number of cancers diagnosed in later stages, where intervention is less successful, should go down. That is, those cancers detected early and treated would not progress and should mean that many fewer women present with later stage cancer.  Unfortunately, this study demonstrates, that has not occurred. The decrease in late-stage cancer diagnosis has been about 8%, or 8 per 100,000 women per year. So, for every 100,000 women, we are diagnosing an additional 122 early stage cancers, but only decreasing the number of late stage cancers by 8. This means that most of the additional women found by mammography to have early stage breast cancer would not have progressed to late-stage cancer. This, then, leads to their assertion that cancer was over-diagnosed – in 70,000 women in 2008 alone. Any estimate of the number of lives saved by screening and early intervention is inflated if it includes large numbers of women whose cancers would not have progressed. In other words, many of these women diagnosed with cancer, many of whom had non-trivial interventions (surgery, radiation chemotherapy) had cancers that would, basically, have not required any treatment.

Some radiologists who do mammograms have said that this is “junk science” (“Study links mammograms to overtreatment”, Boston Globe, November 21, 2012), but it is clearly not; the findings are the findings. The implications, however, are harder to assess. Does this mean women should not get mammograms? No, certainly that would be a premature conclusion. Some of the women diagnosed with early stage breast cancer would have gone on to develop late stage cancer; if you are one of the 8, you are lucky to have been found; if one of the 114, maybe not, especially if you had to endure the potential harms of chemotherapy or radiation or both, not to mention mastectomy. It may suggest that aggressive interpretation of mammography findings are not warranted. What would be useful would be to identify mammographic findings and subsequent pathology findings on biopsy that required aggressive intervention and those that could be safely followed. One type of breast cancer that is likely to be the subject of future studies is that called ductal carcinoma in situ, or DCIS, which may be more likely than some other types to resolve.

It may well be too soon to know the answer on mammographic screening, but it is clear that it is far from the perfect screening test that everyone would like it to be. We need more studies, and more information, and mostly we need a willingness to accept the accumulated findings of research. Certainly, what we do not need is for those who have a financial stake in screening and treatment to call good research “junk science” because it comes to conclusions that they do not like.

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[1] Bleyer A, Welch HG, “Effect of three decades of screening mammography on breast-cancer incidence”, NEJM 22Nov2012;367(21):1998-2005.

MRIs, clinical judgement and access to health care: Where is the money best spent?

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“Sports medicine said to overuse MRIs”, by NY Times health reporter Gina Kolata, October 29, 2011, begins by reporting on an unpublished (as far as I can tell) study by an orthopedic sports medicine physician from Florida, Dr. James Andrews, who scanned the shoulders of 31 asymptomatic, uninjured professional baseball pitchers and found that all were read as “abnormal”. The article goes on to quote a long list of leading sports medicine physicians who find fault with the overuse of MRI scans in both professional and casual athletes. They are particularly concerned that doctors substitute the readings of these scans for history and physical examination and professional judgment. One problem is, according to Dr. Bruce Sangeorzan from the University of Washington, is that the MRI “...is a very sensitive tool, but it is not very specific.” Sensitivity and specificity are terms that refer to the characteristics of a test. The more sensitive a test, the more likely it is to find something that is actually wrong; the more specific the test, the more likely it is to be normal when there is not actually something wrong. Dr. Sangeorzan’s point is that the MRI scan is likely to be abnormal even when there is no actual problem with the person.

This assessment is echoed by most of the physicians interviewed. “‘It is very rare for an MRI to come back with the words “normal study,”’ said Dr. Christopher DiGiovanni, a professor of orthopedics and a sports medicine specialist at Brown University. ‘I can’t tell you the last time I’ve seen it.’” The article profiles a person who injured his knee skiing and had two different doctors tell him that the MRI (ordered even before he was examined) indicated he had a torn anterior cruciate ligament (ACL) and needed surgery. Another orthopedic surgeon, Dr. Freddie H. Fu of the University of Pittsburgh, found he had no tear using a more sensitive MRI – which he ordered because, after seeing the patient, his story and exam was inconsistent with a torn ACL: “He could never have continued skiing with a torn A.C.L. The diagnosis ‘made no sense,’ Dr. Fu said.”

Such overdiagnosis can lead to excess surgery, with all the concomitant risks of these procedures. One concern is the financial conflict of interest that can exist. The physician who reads the MRI gets paid a fair amount, and the owner of the machine (which may be a hospital or a physician or group of physicians, either radiologists or orthopedists) get paid even more for doing the scan. And, if there is surgery, both the surgeon and the facility (hospital or outpatient surgicenter) where it is done make money. The other issue is that both doctors and patients believe that technology is “better” in most cases, and want both a definitive diagnosis and treatment. The danger, of course, is that the diagnosis may wrong and/or the treatment unnecessary.

Many of us have been told by a car mechanic that we needed a repair (new brakes, transmission, valve job), a diagnosis often made with the assistance of computer technology. Sometimes we have brought the car to another mechanic to have the diagnosis confirmed, and sometimes been told that the procedure was not necessary. Then we get angry and believe the first mechanic was a “thief”, out to make money. The reality is, however, that even if they are, all it costs is money; the car may not have needed new brakes quite yet, but the new brakes are not going to harm it. The same is not true for surgical intervention on a knee or shoulder or any other part of the body. Replacing the parts of a human-constructed car is different from cutting into and replacing the parts of a person. While both can have complications from being done badly, surgery on a person can have complications even when done right.

The counterpoints to this article are in the same issue of the NY Times. They are a series of letters addressing “The debate over routine mammograms”, which evidence the fascination that the public has with “making a diagnosis”. Some were written by representatives of advocacy organizations, who repeat the idea that saving a life is worth any cost; “The $5 billion spent annually on mammography screening is worth it to the women who are saved,”, one of these letters declares. This argument is flawed on many levels. Sure, if I am “saved” by having had a mammogram (putting aside, for the moment, any other questions of false-positive tests, treatment options, etc., and assuming the mammogram alone is the reason for my salvation), I am pleased. But $5 billion? Could we have done it for $2.5 billion? Or could we do a better job for $10 billion? Am I unhappy because I had a negative mammogram but the money spent on doing these tests meant that it wasn’t spent on treatments for something I do have, perhaps diabetes, or drug addiction, or for prevention through prenatal care or efforts to ban indoor smoking?

The US Preventive Services Task Force (USPSTF) recommends routine mammogram screening (“screening” means in women who are asymptomatic, and does not include those who have had previous cancer or abnormal mammograms or lumps or bleeding, etc.) every two years. In my hospital, we are trying to set the criteria by which our electronic medical record will remind us to do screening. Initially, we decided to use USPSTF guidelines. But now some physicians are saying that they think we should order mammograms yearly. Oh. If we are not going to use the recommendations based upon the most thorough use of the existing data, why yearly? Why not every six months? Every week? 

Well, in part it is cost. To screen every woman every week would cost a lot. But it would also be inconvenient for those women. And there are, in addition to complications of treatment, results of questionable screening tests to further define what is going on, and these add more costs, discomfort, uncertainty, and risk. I have discussed these issues, with particular emphasis on another screening test that the USPSTF has recommended against using at all, the PSA test for prostate cancer, in recent blogs, most recently PSA redux: The USPSTF finally recommends NOT getting it!, October 14, 2011. For mammography, if less frequent routine screening of everyone with targeted screening of individuals who are at high risk, can have the same positive results without the high costs, both financial and in terms of risk to people, that is a better strategy.

Most important, however, is that arguments such as “The $5 billion spent annually on mammography screening is worth it to the women who are saved,” pretends that such spending occurs in a bubble. There is limited money, and it is getting more limited since the financial crisis and is likely to get worse with the “cut, cut, cut” attitude toward programs for the most vulnerable being the apparent mantra in both Congress and the states. Even in the best times for the economy, there were millions of people not getting the most basic health care, not getting well-established screening tests done, not getting treatments that were proven effective for conditions that they had (and maybe didn’t know they had) because they didn’t have access – insurance, geographic access, access from the perspective of cultural, language and health literacy, whether they were “legal” or many other factors. As these cuts increase, those millions are joined by millions, tens of millions, more. Access for everyone to proven effective interventions must be a priority over access for some to possibly effective interventions, and certainly over access for anyone to those where the danger exceed potential benefit.

The very same issue of the NY Times contains a column by Charles Blow, “America’s exploding pipe dream”, in which his words-to-table ratio is even less than usual, emphasizing the data in the table he attaches. But here are some important words: "We have not taken care of the least among us. We have allowed a revolting level of income inequality to develop. We have watched as millions of our fellow countrymen have fallen into poverty. And we have done a poor job of educating our children and now threaten to leave them a country that is a shell of its former self. We should be ashamed."  Clearing up that shame, taking care of the “least among us”, should be our watchword.

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