Studies of Screening Mammography

Early Questions About Screening Mammograms

An article in the Annals of Internal Medicine in 1976 reviewed existing clinical and experimental data to discern whether screening mammography for entire populations made sense. At the time there was little data on the long-term effects of mammography or the inherent risks associated with radiation. It concluded that “promotion of mammography as a general public health measure was premature, that the possible benefits of mammography received more emphasis than its defects, and that the evidence that mammography alone played a significant role in the reduction of breast cancer mortality was weak and indirect.”

That was almost four decades ago. Since then there have been numerous studies of screening mammography, including randomized clinical trials and statistical modeling, all of which are designed to analyze the impact of routine screening on mortality reduction.

The findings: the vast majority of women (70 to 90 percent) do not have their lives lengthened as a result of routine screening. And there’s a good chance they will be overdiagnosed (5 to 50 percent) and over-treated (20 to 30 percent), sometimes for conditions that are not life-threatening.

Seven Clinical Trials (1963-1982)

A randomized controlled trial (RCT), is a study where people are randomly assigned to receive (or not receive) a particular intervention (i.e., this could be comparing two different treatments, one treatment and a placebo, or a screening group and no-screening group. RCTs are the most reliable type of study design to determine whether an intervention is effective.

Seven major clinical trials were conducted between 1963 and 1982 that involved over half a million women. In 2000 the Lancet published the first systematic review of these trials, which assessed their quality in terms of agreed-upon standards for well-conducted and reliable research and also evaluated the findings. Researchers identified no trials with high-quality data and and two trials that were highly flawed (Edinburgh and New York). The remaining trials had either medium-quality (Canada and Malmö) or poor-quality data (Göteborg, Stockholm, and Two-County).

When taking the methodology into account they concluded that there was no reliable evidence to justify mass screening of entire populations of women.

Meta-Analyses (2001-2006)

The seven clinical trials were evaluated in greater detail and reported in the Lancet in 2001. The best conclusion was that mortality reduction due to routine screening was about 15 percent for women ages 50 to 69. The remaining 85 percent died at the same rate as unscreened women who developed breast cancer.

Two additional meta-analyses of these seven clinical trials (2002 Humphrey review and the 2006 Armstrong review) also concluded that reductions in mortality resulting from mammography screening were quite variable, and fairly modest.

Institute of Medicine Questions Screening Outcomes

The Institute of Medicine (IOM) reviewed breast cancer detection technologies too, releasing a report in 2001 called Mammography and Beyond. These reviewers found that screening outcomes had not been assessed adequately. This confused the potential value of routine mammograms in reducing deaths.

The IOM also identified several problems with the technology. Mammograms are difficult to interpret in women with dense breast tissue (something especially common in pre-menopausal women). Dense tissue interferes with the identification of abnormalities, thereby leading to higher rates of false-positive results (i.e., those that do not, upon biopsy, show the presence of cancer) and also higher false negative results (i.e., those that miss tumors that actually are cancerous). They also found that routine screening frequently gives inconclusive results, and that the ability of current screening tools “to determine the lethal potential of breast abnormalities is crude at best.”

A followup symposium in 2005 reported similar concerns and reiterated that the reduction in the relative risk of dying from breast cancer was somewhere between 20 and 30 percent depending on age at screening.

National Cancer Institute Uses Statistical Models to Evaluate Association Between Screening and Mortality

The National Cancer Institute took up the mammography question in 2005, not through the testing of clinical effectiveness but through the use of high-level statistical modeling. The Cancer Intervention and Surveillance Modeling Network (CISNET) used retrospective surveillance data to create statistical models to illustrate past trends and project future trends related to screening and mortality.

Reports based on CISNET estimated that routine screening reduced mortality between 16 and 22 percent. Based on the confluence of increased screening and improved treatment the researchers concluded that the overall decrease in breast cancer mortality from 1990 to 2000 (i.e., averaging about 20 percent) must have been related to mammography. There is no way to know for sure.

However, statistical modeling for assessing risks and benefits is quite different from using clinical trials that involve real people in comparison groups who are observed over a period of time. Without contextual information about disease profiles, patient demographics, treatment regimens, and quality of care the association between routine screening and the overall decrease in mortality is, unfortunately, only a correlation.

Norwegian Study (2010) Highlights Improvements in Treatment

There had been a general consensus across studies that routine screening reduced the total breast cancer death rate (not the death rate overall) between 15 and 25 percent. However, a Norwegian study reported in the New England Journal of Medicine (2010) found that mammograms combined with modern treatment reduced the death rate by only 10 percent, and that the effect of mammograms alone could be as low as 2 percent or even zero.

This study only included a two-year followup, and must be viewed within its national context. Norwegians are insured under a universal, tax-funded, single-payer health system that is notable in terms of providing an important safety net for the population. The risk of dying of breast cancer is declining in Norway and the current rates are at the same level or lower than European averages.

However, this study illuminates a critical insight: improvements in treatments may be responsible for improved outcomes for some groups of women regardless of when, or how, their tumors were found. Women over age 70 who were exposed to the program’s multidisciplinary medical teams but did not undergo mammography, for example, had an 8 percent reduction in breast-cancer mortality. This would explain why more recent clinical trials in advanced countries with improved treatment regimes are likely to find lesser or no effect on mortality due to screening.

U.S. Preventive Services Task Force (USPSTF) Gives Screening Mammography a Level C Recommendation

The U.S. Preventive Services Task Force (USPSTF) updated its recommendations for breast cancer screening, including a recommendation against routine screening mammography for women ages 40-49 who are not at an increased risk for breast cancer. The Task Force gave routine mammography screening a level C recommendation, “which means that although the USPSTF recommends against routinely providing the service and there is at least moderate certainty that the net benefit is small, there may be considerations that support providing it in an individual patient.

None of this data has had a signficant effect on U.S. society’s overzealous commitment to mammograms. Quarrels that focus on whether to start having them at age 35, 40, or 50 (though important in their own right) serve to detract attention from the fact that the overall reduction in mortality from screening is quite low.

Compare the benefits of routine mammography with that of screening for cervical cancer. The Papanicolaou (Pap) smear has been called “the best screening tool ever introduced for any cancer.” It not only reduces the incidence of cervical cancer by 90 percent by detecting pre-cancerous conditions but has led to a 70 percent reduction in mortality in developed countries. An article in the American Journal of Clinical Oncology reports that among women who are screened regularly, the Pap smear may have reduced cervical cancer mortality by as much as 99 percent.

The success of the Pap smear sets the bar high for breast cancer screening. So far, routine mammography screening hasn’t measured up.

Two Counties in Sweden Suggest that Screening Saves Lives?

Studies abound to find out whether the existing technology benefits a small, or smaller, percentage of women. A study of two counties in Sweden found a mortality benefit of 30 percent. Early detection campaigners were enthusiastic that the study reconfirmed that mammography saves lives. There is much to consider about the Swedish study in the context of the mountains of data that already exist about screening.

First, the findings from the Swedish study were not stratified by age so nothing can be said about the benefits of screening for different age groups of women.

Second, the study did not systematically evaluate outcomes related to false-positive and false-negative results.

Third, the methodology has been questioned previously in terms of the comparison groups and it is not clear that breast cancer deaths were counted correctly.

Fourth, as Dr. H. Gilbert Welch has pointed out the study did not take into account the advances in breast cancer therapy over the last two decades.

Finally, would the Swedish findings be generalizable to a population such as our own that does not have universal healthcare? If all of these issues could be rectified, we would still have a situation in which the vast majority of women routinely screened for breast cancer (in the Swedish study, 70 percent) would see no survival benefit due to screening.

Canadian Study Finds No Reduction in Breast Cancer Deaths Due to Screening Mammograms

One of the largest studies of screening mammography, the Canadian National Breast Screening Study, is a randomized controlled trial (RCT) that compared breast cancer incidence and mortality for women ages 40 to 59 who did, or did not, have an annual screening mammogram. The study followed nearly 90,000 women for up to 25 years. It found that, compared with clinical exam or routine care, annual mammograms did not reduce breast cancer deaths.

Instead of comparing mammography screening to “no screening,” as other studies have done, the Canadian study compared women in the mammography arm to a group of similar women who did not have annual mammograms but did receive comprehensive breast exam (CBE) along with routine care. In fact, women over age 50 in both study groups had CBE. This is important because it shows that screening added no benefit beyond that of good health care and routine clinical breast exam in terms of reducing breast cancer deaths.

The data confirms results from other screening trials that found a very limited benefit for screening, with some studies putting the screening-associated mortality reduction at about 15 percent, or as low as two percent. What these studies suggest, as does the Canadian study, is that quality treatment, rather than annual mammography screening, is responsible for reducing the overall number of breast cancer deaths post-diagnosis.

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