Screening for disease is a real pain. I was reminded of this by the publication of a study in BMJ the very day of the Science-Based Medicine Conference a week and a half ago. Unfortunately, between The Amaz!ng Meeting and other activities, I was too busy to give this study the attention it deserved last Monday. Given the media coverage of the study, which in essence tried to paint mammography screening for breast cancer as being either useless or doing more harm than good, I thought it was imperative for me still to write about it. Better late than never, and I was further prodded by an article that was published late last week in the New York Times about screening for cancer.
If there’s one aspect of medicine that causes more confusion among the public and even among physicians, I’d be hard-pressed to come up with one more contentious than screening for disease, be it cancer, heart disease, or whatever. The reason is that any screening test is by definition looking for disease in an asymptomatic population, which is very different from looking for a cause of a patient’s symptoms. In the latter case, the patient is already being troubled by something that is bothering him. There may or may not be a cause in the form of a disease or syndrome that is responsible for the symptoms, but the very existence of the symptoms clues the physician in that there may be something going on that requires treatment. The doctor can then narrow down range of possibilities for what may be the cause of the patient’s symptoms by taking a careful history and physical examination (which will by themselves most often lead to the diagnosis). Diagnostic tests, be they blood tests, X-rays, or other tests, then tend to be more confirmatory of the suspected diagnosis than the main evidence supporting a diagnosis.
It’s easy to think of medical tests as black and white. If the test is positive, you have the disease; if it’s negative, you don’t. Even good clinicians sometimes fall into that trap. Based on the pre-test probability of the disease, a positive test result only increases the probability by a variable amount. An example: if the probability that a patient has a pulmonary embolus (based on symptoms and physical findings) is 10% and you do a D-dimer test, a positive result raises the probability of PE to 17% and a negative result lowers it to 0.2%.
Even something as simple as a throat culture for strep throat can be misleading. It’s possible to have a positive culture because you happen to be an asymptomatic strep carrier, while your current symptoms of fever and sore throat are actually due to a virus. Not to mention all the things that might have gone wrong in the lab: a mix-up of specimens, contamination, inaccurate recording…
Mammography is widely used to screen for breast cancer. Most patients and even some doctors think that if you have a positive mammogram you almost certainly have breast cancer. Not true. A positive result actually means the patient has about a 10% chance of cancer. 9 out of 10 positives are false positives.
But women don’t just get one mammogram. They get them every year or two. After 3 mammograms, 18% of women will have had a false positive. After ten exams, the rate rises to 49.1%. In a study of 2400 women who had an average of 4 mammograms over a 10 year period, the false positive tests led to 870 outpatient appointments, 539 diagnostic mammograms, 186 ultrasound examinations, 188 biopsies, and 1 hospitalization. There are also concerns about changes in behavior and psychological wellbeing following false positives.
Until recently, no one had looked at the cumulative incidence of false positives from other cancer screening tests. A new study in the Annals of Family Medicine has done just that. (more…)
Last Wednesday, right before the four-day Thanksgiving holiday weekend, as I was far more interested in preparing to have family over the next day than in what was going on in the medical news or the blogs, the results of a most fascinating study hit the news. In Medscape, the title of the news report was Mammography Study Suggests Some Breast Cancer May Spontaneously Regress; on WebMD, the story ran under the title Can Breast Cancer Disappear?; on Medical News Today, Mammograms May Identify Cancers That Would Otherwise Just Regress by Drs. Per-Henrik Zahl, Jan Maehlen, and H. Gilbert Welch. Not surprisingly, the study found its way out of the medical news and into mainstream media outlets as well, given how provocative the findings seemingly are. From the Medscape report on this study:
A mammography study from Norway has come up with the controversial proposal that one fifth of breast cancer detected on screening may spontaneously regress. But there is no easy way to verify whether this is the case, say experts.
The study was published in the November 24 issue of the Archives of Internal Medicine. It found that the cumulative incidence of invasive breast cancer in a cohort of women, aged 50 to 64 years, who received 3 mammograms over 6 years was 22% higher than in a control group of age-matched women who received only 1 mammogram at the end of a 6-year period.
In their review of possible explanations for the difference in the breast cancer rates between the 2 groups — which had similar risk factors for breast cancer — the researchers write that the “natural course for some screen-detected breast cancers may be to spontaneously regress.”
“I anticipate that many clinicians will react negatively to the possibility of spontaneous regression, said coauthor Jan Maehlen, MD, PhD, professor of pathology at the Ulleval University Hospital, in Oslo, Norway, in an interview with Medscape Oncology.
Before I discuss the study itself, let me briefly discuss why clinicians may have a bit of a problem with the implications of this study, if they accurately reflect the biology of breast cancer.