Mortality benefit of screening mammo questioned (again)
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Breast cancer mortality statistics in Sweden appear to confirm studies that have reported minimal or no impact of screening mammography on breast cancer mortality among women aged 40 to 69, according to a study published July 17 in the Journal of The National Cancer Institute. However, two editorial commentaries challenged the researchers’ approach and outlined future directions that move beyond the current debate.

Since 1974, Swedish women aged 40 to 69 have increasingly been offered mammography screening, with nationwide coverage peaking in 1997. Researchers set out to determine if mortality trends would be reflected accordingly. They hypothesized that a mortality reduction would appear first in counties that were early adopters of screening and follow a temporal pattern based on the introduction of screening.

Philippe Autier, MD, of the International Prevention Research Institute in Lyon, France, and colleagues reviewed data from the Swedish Board of Health and Welfare from 1960-2009 to analyze trends in breast cancer mortality in women age 40 and older by the county in which they lived. The researchers compared actual mortality trends with the theoretical outcomes using models in which screening would result in mortality reductions of 10 percent, 20 percent and 30 percent.

The researchers expected that screening would be associated with a gradual reduction in mortality; previous studies, including the Two-County Trial, demonstrated screening reduced mortality in the 23 to 31 percent range.

However, they found that breast cancer mortality rates in Swedish women aged 40 and older started to decline in 1972, prior to the introduction of screening mammography. The rate decreased by 0.98 percent annually from 68.4 to 42.8 per 100,000 from 1972 to 2009.

The downward trend was not completely even in the prescreening and screening periods. “In two counties (Stockholm and Holland), the stronger mortality decrease that we observed could be compatible with an added effect of mammography screening,” Autier et al wrote.

"It seems paradoxical that the downward trends in breast cancer mortality in Sweden have evolved practically as if screening had never existed."

However, they noted certain limitations of the study, including its observational design. Thus, it was unable to take into account the potential influence of other breast cancer risk factors such as obesity, which may have masked the effect of screening on mortality. Population mobility may have biased the results as well, they noted.

Questions persist

In an accompanying editorial, Nereo Segnan, MD, MSc, CPO Piemonte, of the Unit of Cancer Epidemiology at ASO S Giovanni Battista University Hospital in Turin, Italy, and colleagues questioned the use of descriptive analysis to challenge the results of randomized trials and incidence-based mortality studies. “The analysis of time trends of breast cancer mortality rates following the introduction of screening is definitely not the most reliable method to assess its effectiveness.”

They referred to confounders, such as the inclusion of cancers diagnosed before screening started, the phased build-up of screening and the presence of opportunistic screening, which may have impacted the results of this study.

The conclusion by Autier et al that the 37 percent decline in breast cancer mortality in Sweden was not associated with breast cancer screening seems difficult to justify and partially unsupported by data, Segnan et al continued. They referred to the two groups of Swedish Counties which showed a mortality decrease that could be linked to screening.

"It is time to move beyond an apparently never-ending debate on at what extent screening for breast cancer in in the 1970s to 1990s has reduced mortality from breast cancer—as if it was isolated from the rest of health care.”

Segnan and colleagues championed a new model, characterized by “more mature and evidence-based communication.” They also noted the importance of research to identify indolent cancers that may be served by less aggressive treatment and development of protocols to safely reduce the intensity of screening in low-risk women.

In another accompanying editorial, Michael W. Vannier, MD, of the department of radiology at the University of Chicago Medical Center, offered that it's hard to see mortality reduction as a screening benefit because outliers such as the natural history of the disease, along with the frequency of screening and duration of follow-up, may misrepresent the time patterns in the mortality reductions.

He wrote, “Conventional wisdom has been to use mortality as an end point for screening program evaluation, despite the fact that diagnosis, staging, treatment, and retreatment for recurrence take place before the end of life. How much can screening be expected to prolong life given all of the other events that intercede between disease detection and death?” Still, mortality benefit has been used as the primary outcome to assess the effectiveness of a screening program.

According to Vannier, even if screening were 100 percent effective, the number of deaths may remain unchanged. He predicted that without a better alternative, mammography screening will continue to be used. Improved diagnostic tools to evaluate women with screen-detected cancers could address some limits of population-based screening, he concluded.

To learn more about adjuncts to screening mammography, read "Move Over Mammo" in the July/Aug. issue of Health Imaging.

To read about the Swedish Two County Trial, which reported a 30 percent mortality benefit, click here.