CLINICAL QUESTION: Does screening mammography reduce breast cancer mortality?
BACKGROUND: Randomized controlled trials have found that mammography screening for breast cancer reduces mortality. Overall, though, this effect is very small and could have been influenced by very small changes. The 8 randomized studies have evaluated more than 450,000 women, with less than 1% of them dying of breast cancer. In this large group, the difference in mortality in the the screened versus the unscreened groups was only 65 women (837 breast cancer deaths in the screened groups, 902 in the unscreened groups).
Since this difference between the 2 groups is so small, it is crucial that screened and unscreened groups have identical characteristics, so that the initial risk of breast cancer is the same. This study reviewed the methodologic quality of past trials to determine whether methodologic issues could have affected the RESULTS: of these studies.
POPULATION STUDIED: The authors identified 8 randomized controlled clinical trials of screening mammography. To evaluate the studies for the meta-analysis, they carefully scrutinized the methodology of these studies. The reviewers focused primarily on how the researchers concealed the assignment to the groups so that no one knew in advance whether the next woman to be entered in the study would be randomized. If this concealment occurred properly, the randomized groups should have similar characteristics.
OUTCOME MEASURED: The primary focus of this analysis was whether the methodology of the studies, rather than a beneficial effect of mammography screening, could have accounted for the difference in mortality. The analysis compared risk of mortality—both due to any cause and due to breast cancer—in trials with and without appropriate randomization methods.
RESULTS: he authors concluded that 6 of the 8 trials used a process of randomization that failed to produce similar groups. One trial enrolled women in pairs but somehow ended up with unequal numbers of women in the 2 groups. In another trial, approximately twice as many women in the screened group were in the highest socioeconomic stratum, an imbalance that should not have occurred if the enrollment was truly random. One trial enrolled significantly fewer women in the screened group who had a preexisting breast lump. All of these imbalances suggest that the 2 groups being compared were not truly comparable. In one trial, women who were not screened were an average of 6 months older than those who received screening, a statistically significant and important difference when the outcome being considered is mortality rate.
In addition, 4 of the 6 trials failed to account consistently for the patients enrolled in their study. Patients initially enrolled in the study were not included in the final analysis, presumably because of administrative problems with managing the patient database.
These 6 flawed studies are the ones that support the usefulness of mammography screening. Breast cancer-related deaths were significantly lower in the screened group (relative risk [RR]=0.75; 95% confidence interval [CI], 0.67-0.83).
Two trials used adequate randomization and accounted for all of the enrolled women. Those 2 trials also used masked assessment of the cause of death, eliminating another source of potential bias. The combined data from those 2 trials showed no effect of screening on breast cancer mortality (RR=1.04; 95% CI, 0.84-1.27) or on total mortality (RR=0.99; 95% CI, 0.94-1.05).
Three trials evaluated the effect of mammography on overall mortality rates. All-cause mortality was not significantly affected by mammography screening. Two trials evaluated morbidity, finding surgery and radiotherapy to be performed more frequently in the screened patients. Also, benign findings in biopsy samples were reported 2 to 4 times more frequently in the screened patients.
This study casts an important doubt on the methodologic quality of studies purporting to show a benefit of screening mammography. Studies that started with truly equal groups show no benefit to screening. However, prevailing politics, patients’ preconceptions, and the fear of litigation are likely to counterbalance the results of this study. The best approach to offering mammograms to women of any age will be to give them the current facts regarding mammography screening: (1) one of every thousand women screened by mammography may be prevented from dying of breast cancer, although there may not be a benefit at all; (2) mammography screening has never been shown to help women to live longer; and, (3) half of the women who receive yearly mammograms for 10 years will have a false-positive result, and 19% will be subjected to biopsy.