Diagnosis of Additional Small Cancers Suggests Screening Mammography Leads to Overdiagnosis

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A study of screening mammography across U.S. counties found that “the clearest result of mammography screening is the diagnosis of additional small cancers” but without a “concomitant decline in the detection of larger cancers, which might explain the absence of any significant difference in the overall rate of death from the disease. Together, these findings suggest widespread overdiagnosis,” the study investigators wrote in JAMA Internal Medicine.

The investigators included lead author Charles Harding, AB, in private practice in Seattle; corresponding author Richard Wilson, DPhil, Department of Physics, Harvard University, Cambridge; and H. Gilbert Welch, MD, MPH, Department of Medicine, Dartmouth Institute for Health Policy and Clinical Practice, Hanover, New Hampshire. Dr. Welch has previously been interviewed by The ASCO Post concerning cancer screening and is coauthor of the book Overdiagnosed: Making People Sick in the Pursuit of Health.

Key Data

The researchers analyzed data on 6 million women 40 years or older who resided in 547 counties reporting to the Surveillance, Epidemiology, and End Results (SEER) cancer registries during the year 2000. “Of these women, 53,207 were diagnosed with breast cancer that year and followed up for the next 10 years,” the researchers reported. The extent of screening in each county was assessed as the percentage of included women who reported receiving a screening mammogram in the prior 2 years. The incidence of breast cancer, including ductal carcinoma in situ, in 2000 and incidence-based breast cancer mortality during the 10-year follow-up were calculated for each county and age adjusted to the U.S. population.

“Across [the United States], there was a positive correlation between the extent of screening and breast cancer incidence (weighted r = 0.54; P < .001) but not with breast cancer mortality (weighted r = 0.00; P = .98). An absolute increase of 10 percentage points in the extent of screening was accompanied by 16% more breast cancer diagnoses (relative rate [RR], 1.16; 95% confidence interval [CI], 1.13–1.19) but no significant change in breast cancer deaths (RR, 1.01; 95% CI, 0.96–1.06),” the researchers reported.

“In an analysis stratified by tumor size, we found that more screening was strongly associated with an increased incidence of small breast cancers (≤ 2 cm) but not with a decreased incidence of larger breast cancers (≥ 2 cm). An increase of 10 percentage points in screening was associated with a 25% increase in the incidence of small breast cancers (RR, 1.25; 95% CI, 1.18–1.32) and a 7% increase in the incidence of larger breast cancers (RR, 1.07; 95% CI, 1.02–1.12),” the authors added.

“The simplest explanation” of the observed data “is widespread overdiagnosis, which increased the incidence of small cancers without changing mortality, and therefore matches every feature of the observed data,” the investigators stated.

A Closer Look at Ecologic Studies

“Clinicians are correct to be wary of ecological studies because of the ecological fallacy,” referring to making inferences about individuals from group data in statistical analyses, the authors acknowledged.

“Ecological studies use an intuitively appealing research design that relates the frequency with which some exposure or intervention (eg, cancer screening) and some outcome of interest (eg, cancer diagnosis or mortality) occur in the same geographic area or care setting,” noted an accompanying editorial. The authors of that editorial are Joann G. Elmore, MD, MPH, University of Washington School of Medicine, and Ruth Etzioni, PhD, Fred Hutchinson Cancer Research Center, Seattle.

The authors noted that ecological studies have been helpful throughout the years in identifying associations between smoking and subsequent lung cancer and Pap tests and cervical cancer. “However, much has also been written about the caution needed when interpreting ecological analyses,” the editorialists added.

“It is well known, for example, that ecological studies provide no information as to whether the people who were actually exposed to the intervention were the same people who developed the disease, whether the exposure or the onset of disease came first, or whether there are other explanations for the observed association. Ecological analyses also may not properly reflect group-level associations because of area-level variations in confounding factors or other practices affecting the outcome.”

The editorialists pointed out that the ecological study design used merged two large data sources, the SEER incidence and mortality data, and the “county-level estimates of mammography, based on national surveys of women who recount prior mammography examinations.” They also noted that “prior ecological studies of mammography conducted at the larger state level with a wider range of mammography frequencies showed a decline in breast cancer mortality associated with more screening.”

Communicating About Uncertainty

With no definitive answers about the percentages of overdiagnosis among women receiving screening mammography and which women are diagnosed with ductal carcinoma in situ or invasive cancers, “we need clear communication and better tools to help women make informed decisions regarding breast cancer screening mammography,” Drs. Elmore and Etzioni wrote.

“Perhaps most important, we need to learn how to communicate with our patients about uncertainty and the limits of our scientific knowledge. In the end, we all need to become comfortable with informing women that we do not know the actual magnitude of overdiagnosis with precision. Part of informed decision making is providing all the information, even our uncertainty.” ■

Harding C, et al: JAMA Intern Med 175:1483-1489, 2015.

Elmore JG, Etzioni R: JAMA Intern Med 175:1490-1491, 2015.