Controversial mammography study opens door for new thinking

The recent report from the Canadian National Breast Screening Study (CNBSS) that concluded that mammography screening does not reduce deaths from breast cancer has sparked new thought on how to frame issues associated with breast cancer screening, as evidenced by two commentaries published on April 7 in Annals of Internal Medicine.

The first commentary, entitled “Screening Is Only Part of the Answer to Breast Cancer,” by Russell Harris, MD, MPH, of the University of North Carolina Health Care in Chapel Hill, makes the assertion that the way in which society thinks about breast cancer needs to be refocused to look at the larger issue at hand: reducing the burden of suffering that breast cancer brings to society.

Harris urges the community to glean two messages from the CNBSS study: that annual mammography did not reduce breast cancer deaths for women between the ages of 40 to 59 when compared with women who did and did not have clinical breast examinations, and that overdiagnosis is real.

The first finding counters that of the U.S. Preventive Services Task Force (USPSTF), as they revealed in trials from the 1970s and 80s that mammography led to a 15 percent relative risk reduction in women between the ages of 40 and 49 and a 16 percent reduction in women between the ages of 50 and 59. Though several factors could explain this stark difference in discoveries, Harris argues that the underlying message of both is the same.

“For women aged 40 to 59 years, screening mammography reduces breast cancer deaths, at best, to only a small degree. Although the USPSTF review found a greater benefit for women aged 60 to 69 years, that estimate, based on only 2 trials, was less certain. A policy of screening for women aged 60 to 69 years every 2 years may provide the best tradeoff between benefits and harms,” he wrote.

In terms of Harris’s second point, overdiagnosis is the cause of at least 22 percent of cases of screen-detected invasive cancer. Despite the controversy that is attached to this finding, Harris believes that mammography likely adds little to reducing breast cancer deaths for women between 40 and 59, but could add more for those between 60 and 69.

“The harms of overdiagnosis are substantial, giving us further pause about the wisdom of screening mammography. If we hear the messages, we may begin to witness the slow scaling back of what has been our greatest hope for reducing the burden of suffering due to breast cancer: screening mammography,” he wrote.

To reframe the issue, the author suggests thinking beyond trials to consistent and known epidemiologic associations with breast cancer, such as obesity and level of physical activity.

“We do not have trial evidence about these lifestyle practices, but we do have consensus that there are multiple reasons to avoid obesity and to be physically active. Let us begin thinking of these activities as reducing risk not only for cardiovascular disease and other conditions but also for breast cancer,” he wrote.

While Harris argues for the reframing of the way in which screening is perceived and pushes for a shift toward more focus on the epidemiologic associations of breast cancer, Peter Jüni, MD, and Marcel Zwahlen, PhD, both of the University of Bern in Switzerland, believe that a new kind of breast cancer screening study is necessary in their commentary, “It Is Time to Initiate Another Breast Cancer Screening Trial.”

In light of controversy that has cropped up over both the CNBSS and a technology assessment issued by the Swiss Medical Board,  Jüni and Zwahlen reexamined the Canadian trials by using death from causes other than breast cancer as a marker of proper trial design and conduct.

“Mammography provides diagnostic information about the breast, but it does not incidentally detect treatable causes of death in other organs,” wrote the authors. “Therefore, screening mammography should, if effective, reduce breast cancer deaths but not deaths from other causes.”

After plotting the estimated effects of mammography screening on deaths from causes other than breast cancer against the statistical precision of the screening trials, the researchers found a 15 percent reduction in breast cancer deaths and a null result for deaths attributed to other causes in consistent trials. Inconsistent trials exhibited a 29 percent reduction in breast cancer deaths and an overall pooled relative risk of deaths from other causes with screening of 0.96.

Consistent trials had a relative risk of 1.00 for all-cause mortality, a narrow confidence interval that ranged from 0.97 to 1.09, and no heterogeneity. Inconsistent trials, on the other hand, had an imprecise pooled relative risk of 0.94 and large heterogeneity. 

“Taken together, these analyses do not provide any evidence for an effect of mammography screening on all-cause mortality—the most definite measure of the net benefit of mammography,” write Jüni and Zwahlen.

The first mammography screening trial is archaic, as more than 50 years have passed since it was initiated.

“Endless rehashing of data from old trials cannot provide definitive answers to these questions,” they wrote. “The only way to know for certain is to initiate a new trial in the era of contemporary screening technologies and breast cancer therapies.”