Saturday, October 30, 2010

Breast cancer screening: conflicting evidence? what are the important questions for health?

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Several new, and sometimes contradictory, studies about breast cancer and screening mammography have recently appeared in the medical literature. In a recent study from Norway, published in the New England Journal of Medicine, Kalager et. al[1] looked at the impact of mammography screening of women 50-69 years old in that country by comparing groups of women who were screened and those who were not screened between 1996 and 2005 and comparing them both with comparable groups for the 1986-1995 period. They discovered a significant decrease in the rate of breast cancer detected in women who were screened – but also in women who were not screened. The decrease was greater in the women who were screened, but this only accounted for 1/3 of the reduction in breast cancer mortality in that group; while the reductions in each group were statistically significant, the difference between them was not (quite). Overall the reduction in the death rate in screened women was 7.2 per 100,000 woman-years, and in the non-screened group 4.8 per 100,000 woman-years.

Meanwhile, Cancer published an article from Sweden looking at mammography screening for women who were 40-49 years of age. Because not all Swedish counties screened women that age, they were able to do a retrospective comparison between those counties who began screening at 40 compared to those counties who began at 50. Hellquist, et. al.,[2] found a significant risk reduction (a relative risk of 0.74 for women invited to screening and of 0.71 for those actually screened). Over 16 years of the study “…there were 803 breast cancer deaths in the study group (7.3 million person-years) and 1238 breast cancer deaths in the control group (8.8 million person-years)”, or converting to the same units as the other study, a reduction of 3 deaths per 100,000 woman years, from 14 to 11. The authors note that 1252 women this age would need to be screened to prevent one death.

The Swedish study provides data to support screening women at 40 (although the reduction was greatest in the 45-49 group, which is not surprising as the incidence of breast cancer increases with age). The Norwegian study shows that the rate of breast cancer has decreased anyway. The Swedish study is not a randomized controlled trial, but rather solely a historical comparison, and thus did not control for differences between the women who got screening and those who did not that might have affected breast cancer risk.

So which are we to believe? Both, to the extent that we can understand the methods used. The question is what are we to do? “We”, here, being both women who might choose to undergo mammography screening, and doctors who have to decide whether to recommend it, especially to those under the age of 50. For me, it will involve discussions with each woman, dependent on her individual risks and preferences. The population health benefit is small but significant; while for any woman the risk reduction might be of value regardless of the cost, that woman (and everyone else) has to also bear the cost of screening all those women – 1252 to save the life of one woman 40-49 in the Swedish study. Clearly, women who have a higher risk (family history) will benefit more, since they are more likely to have breast cancer than those without such a family history.

The cost is not only all those mammograms, but the cost of further tests (additional views or ultrasound) in women with questionable results (more common in younger women who on average have denser breasts), in biopsies – not without risk, though low – and pathology reports, discomfort etc. Not to mention what that money might otherwise be spent on. Feeding the homeless? Providing prenatal care? Fighting HIV/AIDS? Building more bombs? Bailing out big financiers? I would certainly agree that there are social programs that could more effectively use the money currently being spent to screen low-risk younger women for breast cancer with far more social benefit; I would also acknowledge the very low likelihood of any saving in mammography screening being used for such purposes rather than other high-tech medical care or further health system profit.

A more important question, perhaps, is why, at any age level, are certain parts of the population – poorer and minority women – less likely to be screened? To the extent that screening does detect cancer in earlier stages, when intervention can be done, and thus make a difference in mortality, why is it not being done as effectively with minority women? For example, African American women are less likely to get breast cancer, but more likely to die from it.

But people do want “answers”, definitives. Newspapers like to publish “breakthrough” research that seems to provide them. When the “answers” seem contradictory, it leads to frustration for many, and a decision to do what they had planned to do anyway, to do what seems to make “sense” (and what they can afford). After all, if sometimes we hear that Vitamin C or E or beta-carotene is a wonder drug to prevent cancer, or Alzheimer’s, and later studies show that it isn’t, and sometimes may even create greater risk, what are we to do?

One thing we could choose to do is to listen to those who are sure that they have the answers, even when these are based upon no data or carefully-selected data. If someone advises people based upon a single study, regardless of the scientific quality of that study and how often its results might have been refuted by later studies, they can be more confident and sure of themselves. This can inspire confidence on those they advise. (I am reminded of the story told by a colleague, fresh out of residency, who was practicing with farmworkers in the Imperial Valley of California. These folks, he said, are used to going to a doctor who listens to their problem, nods, tells them what they have, and gives them a shot to fix it. “I,” he noted, “listen, then tell them to take off all their clothes, examine them for a long time, and then finally tell them I’m not sure what it is, but it probably doesn’t need a shot – and that the shot might even be bad for them – and likely it will go away with time. Who are they going to trust?”). Showing confidence in your opinion is very persuasive. Thus the term “confidence men” (now shorted to “con”).

By the way, I don’t think this is such a good choice. That studies may seem contradictory is part of the nature of science, of how the studies were conducted, on whom, with what controls, using what methods. A future blog will discuss the work of Dr. John Ioannidis, whose work has raised questions about how much of the work published as research is true, made recently au courant by David H. Freedman’s article in the November Atlantic “Lies, damned lies, and medical science,” and some of the important lessons to be learned – and not learned – from his work. Nonetheless, this confusion does not justify complete nihilism – do whatever you want and it’s all the same – or much less undertaking treatments that have never really been studied. (See Drugs, Tobacco, Doctors and the Health of the Public, September 10, 2010.)

In the meantime, remember that there are probably not too many magic shortcuts to better health. A healthful diet and more exercise will make you fitter and stronger and able to do more things; reading and thinking and doing puzzles are interesting, stimulating and fun, whether they prevent Alzheimer’s disease or not.

[1] Mette Kalager, M.D., Marvin Zelen, Ph.D., Fr√łydis Langmark, M.D., and Hans-Olov Adami, M.D., Ph.D, Effect of Screening Mammography on Breast-Cancer Mortality in Norway, N Engl J Med 2010; 363:1203-1210.

[2] Hellquist BN, et. al., Effectiveness of population-based service screening with mammography for women ages 40 to 49 years, Cancer published online Sept 29 ,2010
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