Mammogram Calls into Question Breast Cancer Natural History

The findings of a Norwegian study recently published in Archives of Internal Medicine suggest that “the natural course of some screen-detected invasive breast cancers is to spontaneously regress.”

Researchers, led by Per-Henrik Zahl, MD, PhD, Norwegian Institute of Public Health, Oslo, Norway, examined breast cancer rates for 119,472 women age 50 to 64 who were invited to receive three rounds of screening mammograms between 1996 and 2001, compared their rates to a control group of 109,784 women in the same age group in 1992, and tracked cancers for six years using a national registry. They found that cancer rates significantly increased in women who underwent mammography every two years (1,909 per 100,000 women) compared to the control group (1,564 per 100,000 women), as anticipated. However, even after prevalence screening in controls, “the cumulative incidence of invasive breast cancer remained 22 percent higher in the screened group,” the authors wrote, suggesting that some cancers detected by mammography may have regressed spontaneously without having been discovered and treated.

“Although many clinicians may be skeptical of the idea, the excess incidence associated with repeated mammography demands that spontaneous regression be considered carefully,” the authors wrote. “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 authors noted that their findings don’t address the question of whether mammograms prevent death from breast cancer, but instead, “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.”

In an editorial response to the article in the same issue of Archives of Internal Medicine, Robert M. Kaplan, PhD, University of California, Los Angeles, and Franz Porzsolt, MD, PhD, Clinical Economics University of Ulm, Germany, stated that 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. 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.”

The study authors agree. “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 concluded.