Does mammography equal over-diagnosis?

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Screening mammography was associated with increased diagnosis of small cancers in a study across US counties but not with significant changes in breast cancer deaths or a decreased incidence of larger breast cancers, which researchers suggest may be the result of over-diagnosis, according to new research.

The goal of screening mammography is to reduce breast cancer death by detecting and treating cancer early in the course of the disease. If screening detects tumours early, the diagnosis of smaller and more treatable cancers should increase, while the diagnosis of larger and less treatable cancers should decrease. However, there are increasing concerns that screening unintentionally leads to over-diagnosis by identifying small, indolent or regressive tumours that would not otherwise become clinically apparent.

Dr Richard Wilson, of Harvard University and co-authors conducted an ecological study of 16m women ages 40 and older who lived in 547 counties reporting to Surveillance, Epidemiology and End Results 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 authors examined the extent of screening in each county and measured breast cancer incidence in 2000 and incidence-based breast cancer death during the 10-year follow-up, with incidence and mortality calculated for each county.

The authors found that across counties there was a correlation between the extent of screening and breast cancer incidence but not with breast cancer mortality. An increase of 10 percentage points in the extent of screening was associated with 16% more breast cancer diagnoses but not significant change in breast cancer deaths.

More screening also was associated with increased incidence of small breast cancers of 2cm or less but not with a decreased incidence of larger breast cancers, according to the results. An increase of 10 percentage points in screening was associated with a 25% increase in the incidence of small breast cancers and a 7% increase in the incidence of larger breast cancers.

“Across US counties, the data show that the extent of screening mammography is indeed associated with an increased incidence of small cancers but not with decreased incidence of larger cancers or significant differences in mortality. What explains the observed data? The simplest explanation is widespread over-diagnosis, which increases the incidence of small cancers without changing mortality, and therefore matches every feature of the observed data,” the authors conclude.

However, the authors note clinicians are correct to be wary of ecological studies because of ecological fallacy, which is making inferences about individuals from group data in statistical analyses because individuals may not possess those characteristics. “As is the case with screening in general, the balance of benefits and harms is likely to be most favourable when screening is directed to those at high risk, provided neither too frequently nor too rarely, and sometimes followed by watchful waiting instead of immediate active treatment,” the study concludes.

Abstract
Importance: Screening mammography rates vary considerably by location in the United States, providing a natural opportunity to investigate the associations of screening with breast cancer incidence and mortality, which are subjects of debate.
Objective: To examine the associations between rates of modern screening mammography and the incidence of breast cancer, mortality from breast cancer, and tumor size.
Design, Setting, and Participants: An ecological study of 16 million women 40 years or older who resided in 547 counties reporting to the Surveillance, Epidemiology, and End Results 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 study covered the period January 1, 2000, to December 31, 2010, and the analysis was performed between April 2013 and March 2015.
Exposures: Extent of screening in each county, assessed as the percentage of included women who received a screening mammogram in the prior 2 years.
Main Outcomes and Measures: Breast cancer incidence in 2000 and incidence-based breast cancer mortality during the 10-year follow-up. Incidence and mortality were calculated for each county and age adjusted to the US population.
Results: Across US counties, 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% CI, 1.13-1.19) but no significant change in breast cancer deaths (RR, 1.01; 95% CI, 0.96-1.06). 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).
Conclusions and Relevance: When analyzed at the county level, the clearest result of mammography screening is the diagnosis of additional small cancers. Furthermore, there is no 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 over-diagnosis.

JAMA material
JAMA Internal Medicine abstract
JAMA Internal Medicine commentary


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