Some Tumors Identified by Mammograms Would Have Naturally Regressed

Breast cancer rates increased considerably in four Norwegian counties after women there began undergoing mammography every two years, according to new research.

Rates among routinely 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 tumors detected by mammography may have spontaneously regressed had they not been discovered and treated.

Throughout Europe, the initiation of screening mammography programs has been associated with increased incidence of breast cancer, according to the researchers. "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 wrote in their article, published in the November 24, 2008, issue of the journal Archives of Internal Medicine. "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., from the Norwegian Institute of Public Health (Oslo) and colleagues assessed 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. Tumors 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 predicted, 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% higher in the screened group,” the investigators reported. Of every 100,000 women screened, 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 researchers reported in their study. "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."

According to the researchers, spontaneous regression of invasive breast cancer has been reported with a recent research identifying 32 reported cases. This is a comparatively small number given such a common disease. However, as some observers have pointed out, the fact that validated observations are rare does not mean that regression rarely occurs. It may instead reflect the fact that these tumors are rarely allowed to follow their natural course.

The findings do not answer the question of whether mammograms prevent deaths from breast cancer, the investigators noted. "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 concluded.

In an editorial commenting on the study published in the same issue of the Archives of Internal Medicine, 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, wrote, "Despite the appeal of early detection of breast cancer, uncertainty about the value of mammography continues. In this issue of the Archives, Zahl et al use a clever study design in an attempt to estimate the value of screening.”

They continued stating that possibly the most significant concern raised by the study is that it highlights how amazingly little doctors know about what happens to untreated patients with breast cancer. Drs. Kaplan and Porzsolt continued, "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.”

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Norwegian Institute of Public Health