Breast cancer rates increased significantly in four Norwegian counties after women there began undergoing mammography every two years, according to a report in the November 24 issue of Archives of Internal Medicine, one of the JAMA/Archives journals. Rates among regularly screened women remained higher than rates among women of the same age who were screened only once after six years, suggesting that some of the cancers detected by mammography may have spontaneously regressed had they not been discovered and treated.

Throughout Europe, the start of screening mammography programs has been associated with increased incidence of breast cancer, according to background information in the article. "If all of these newly detected cancers were destined to progress and become clinically evident as women age, a fall in incidence among older women should soon follow," the authors write. "The fact that this decrease is not evident raises the question: What is the natural history of these additional screen-detected cancers?"

Per-Henrik Zahl, M.D., Ph.D., of the Norwegian Institute of Public Health, Oslo, and colleagues examined breast cancer rates among 119,472 women age 50 to 64 who were all invited to participate in three rounds of screening mammograms between 1996 and 2001 as part of the Norwegian Breast Cancer Screening Program. They compared these to rates among a control group of 109,784 women age 50 to 64 in 1992, who would have been invited for screening if the program had existed at that time. Cancers were tracked for six years using a national registry, and at the end of that time all participants were invited to undergo a one-time screening to assess breast cancer prevalence.

As anticipated, breast cancer rates were higher among screened women than among the control group before the final prevalence screening. "Even after prevalence screening in controls, however, the cumulative incidence of invasive breast cancer remained 22 percent higher in the screened group," the authors write. Of every 100,000 screened women, 1,909 had breast cancer during the six-year period, compared with 1,564 of every 100,000 in the control group. Screened women were more likely to have breast cancer at every age.

"Because the cumulative incidence among controls never reached that of the screened group, it appears that some breast cancers detected by repeated mammographic screening would not persist to be detectable by a single mammogram at the end of six years," the authors write. "This raises the possibility that the natural course of some screen-detected invasive breast cancers is to spontaneously regress."

"Although many clinicians may be skeptical of the idea, the excess incidence associated with repeated mammography demands that spontaneous regression be considered carefully," they continue. "Spontaneous regression of invasive breast cancer has been reported, with a recent literature review identifying 32 reported cases. This is a relatively small number given such a common disease. However, as some observers have pointed out, the fact that documented observations are rare does not mean that regression rarely occurs. It may instead reflect the fact that these cancers are rarely allowed to follow their natural course."

The findings do not answer the question of whether mammograms prevent deaths from breast cancer, the authors note. "Instead, our findings simply provide new insight on what is arguably the major harm associated with mammographic screening, namely, the detection and treatment of cancers that would otherwise regress," they conclude.

"Despite the appeal of early detection of breast cancer, uncertainty about the value of mammography continues," write Robert M. Kaplan, Ph.D., of the University of California, Los Angeles, and Franz Porzsolt, M.D., Ph.D., of Clinical Economics University of Ulm, Germany, in an accompanying editorial. "In this issue of the Archives, Zahl et al use a clever study design in an attempt to estimate the value of screening."

"Perhaps the most important concern raised by the study by Zahl et al is that it highlights how surprisingly little we know about what happens to untreated patients with breast cancer," Drs. Kaplan and Porzsolt continue. "In addition to not knowing the natural history of breast cancer for younger women, we also know very little about the natural history for older women. We know from autopsy studies that a significant number of women die without knowing that they had breast cancer (including ductal carcinoma in situ). The observation of a historical trend toward improved survival does not necessarily support the benefit of treatment."

"If the spontaneous remission hypothesis is credible, it should cause a major re-evaluation in the approach to breast cancer research and treatment. Certainly it is worthy of further evaluation," they conclude.

This study was supported in part by a Research Enhancement Award from the Department of Veterans Affairs.