When women in four Norwegian countries began regular mammography every two years, breast cancer rates increased significantly, and this suggests that the mammography may have be detecting cancers that might have spontaneously regressed, according to an article released on November 24, 2008 in the Archives of Internal Medicine, one of the JAMA/Archives journals.
The start of regular screening through mammography in Europe was associated in increased incidence of breast cancer — this is a relatively normal consequence of any new screening program. However, the authors note, “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.” They continue, noting that this has not occurred: “The fact that this decrease is not evident raises the question: What is the natural history of these additional screen-detected cancers?”
To investigate the etiology of these newly identified cancers, Per-Henrik Zahl, M.D., Ph.D., of the Norwegian Institute of Public Health, Oslo, and colleagues observed breast cancer rates in women who were invited to participate in three rounds of screening mammograms between 1996 and 2001 in the Norwegian Breast Cancer Screening Program. A total of 119,472 women between the ages of 50 and 64 participated.
The rates in these women were compared to a control group in the same age range in 1992 who would have been invited for screening, if the program had existed in that year. National registries were used to track cancer rates. At the end of six years, these control women were invited to participate in a one-time screen for cancer prevalence.
Breast cancer rates were higher in the screened population than in the control group — this was expected, as they were being checked more regularly. However, when the control group was screened, the total number of cancer diagnoses in the control population was lower than those in the screened group. “Even after prevalence screening in controls, however, the cumulative incidence of invasive breast cancer remained 22 percent higher in the screened group,” write the authors.Over the course of the six years, 1,909 of the screened women in every 100,000 had breast cancer. In contrast, 1,564 of every 100,000 women in the control group had breast cancer. This was also true for every stratified age.
The authors give a potential explanation for these absent cancers: “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,” they say. “This raises the possibility that the natural course of some screen-detected invasive breast cancers is to spontaneously regress.”
They continue: “Although many clinicians may be skeptical of the idea, the excess incidence associated with repeated mammography demands that spontaneous regression be considered carefully.” They add that this is not an unlikely scenario: “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.”
Their findings cannot make a statement about mammograms’ ability to prevent breast cancer deaths, they say. “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.”
Robert M. Kaplan, Ph.D., of the University of California, Los Angeles, and Franz Porzsolt, M.D., Ph.D., of Clincal Economics University of Ulm, Germany, contributed an accompanying editorial that notes that lack of knowledge which still persists about the natural history of breast cancer. “Despite the appeal of early detection of breast cancer, uncertainty about the value of mammography continues,” they write. “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,” they 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 finally conclude.
The Natural History of Invasive Breast Cancers Detected by Screening Mammography
Per-Henrik Zahl, MD, PhD; Jan Mæhlen, MD, PhD; H. Gilbert Welch, MD, MPH
Arch Intern Med. 2008;168(21):2311-2316.
The Natural History of Breast Cancer
Robert M. Kaplan, PhD; Franz Porzsolt, MD, PhD
Arch Intern Med. 2008;168(21):2302-2303.
Written by Anna Sophia McKenney