In his recent article, “Screening Mammography: Update and Review of Publications Since Our Report in the New England Journal of Medicine on the Magnitude of the Problem in the United States,” Dr. Archie Bleyer attempts to amass data from multiple studies to strengthen his case for the clinical relevance of the concept of overdiagnosis of breast cancers detected by screening mammography. In doing so, he illustrates one of the fundamental problems with the topic. Because there are no studies that directly measure the existence, extent, and effect of overdiagnosis of breast cancer, one is left with widely disparate estimates of “overdiagnosed” breast cancers (0–70%). This disparity occurs because all of the information on overdiagnosis is simply an estimate—at best, a projection based on rigorous calculation and extrapolation from existing data (including randomized controlled trials and cancer registries), and at worst, only a “best guess,” to use Bleyer’s verbiage.
The estimates of overdiagnosis (Bleyer’s “best guess, extreme assumption, and very extreme assumption”) in his current article and in his earlier article in the New England Journal of Medicine were derived from the Surveillance, Epidemiology, and End Results database. Bleyer states that “…the US has been screening nationally for more than three decades in more than 60% of women older than 40 at yearly intervals.” However, in the Surveillance, Epidemiology, and End Results database, women who were undergoing screening and diagnostic mammography were grouped together and actually only approximately 50% have been undergoing screening mammography every 2 years. In addition, the increase in breast cancer incidence in women under 40 (their surrogate for unscreened women) was extrapolated to make incidence predictions for women over 40, although the relationship of incidence in women at different ages to that in younger women is not clearly established. Other investigators have demonstrated that baseline breast cancer rates have increased five to six times faster than Bleyer and Welch estimated in their article. Using these other data, a 37% reduction in late-stage cancer was demonstrated and the issue of overdiagnosis was markedly reduced.
Just as there is little evidence that untreated breast cancers can spontaneously resolve, there are also no trials that directly test the hypothesis of breast cancer overdiagnosis. To answer this question, one might, for example, design a study in which patients diagnosed with breast cancer were randomly assigned to one of two arms (one in which patients receive standard treatment and one in which patients receive no treatment). Then, the two groups would be followed over a period of time and breast cancer mortality would be measured and compared. Patients who did not ultimately succumb to breast cancer in the treatment arm would be considered to have been “overdiagnosed.” It is hard to imagine that such a study design would pass ethical muster for an institutional review board or, even if approved, that it would accrue many patients.
Finally, Dr. Bleyer makes the reasonable statement, “Ultimately, we need better screening procedures and bio-pathologic, genomic, and other molecular/cellular features that predict who really has cancer and needs to treated.” This accurately outlines the situation at the present time and appropriately underlines the fact that it is not currently possible to determine which cases of breast cancer, if left untreated, will progress and result in the patient’s death. To deprive patients of potentially life-saving treatments while we wait for science to play catch-up and provide answers is unethical. Until the future state of breast cancer diagnosis and treatment envisioned by Dr. Bleyer becomes reality, one is left to wonder what clinical utility this debate about overdiagnosis serves.
References
1. Bleyer A., Welch H.G.: Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med 2012; 367: pp. 1998-2005.
2. Helvie M.A., Chang J.T., Hendrick R.E., et. al.: Reduction in late-stage breast cancer incidence in the mammography era: implications for overdiagnosis of invasive cancer. Cancer 2014; 120: pp. 2649-2656.