Breast cancer screening can sometimes identify cancers that would never have caused symptoms or threatened a woman's health during her lifetime—a phenomenon known as overdiagnosis, which has long been considered one of the potential drawbacks of screening. 
For decades, researchers have debated how often overdiagnosis actually occurs, with estimates from randomized trials differing sharply and some studies suggesting that 30-50% of breast cancers detected through screening could fall into this category, figures that have influenced international discussions about both the benefits and possible harms of population-based breast cancer screening. 
"The aim of our study was to bring together the evidence from all randomized controlled trials to get a clearer picture of the extent of overdiagnosis in breast cancer screening," says Sisse Helle Njor, professor at University of Southern Denmark and Lillebælt Hospital, who continues. 
"Randomized trials have often been cited as evidence that overdiagnosis is a substantial problem. Our study shows that this interpretation is not as straightforward as it may seem." 
To investigate the issue, the team combined and reanalyzed results from all eight randomized trials of mammography screening the New York Health Insurance Plan, Malmö, Two-County, Edinburgh, the Canadian National Breast Screening Study, Stockholm, Gothenburg, and UK Age and compared them with data from two regional screening programs in Denmark, examining both invasive breast cancer and ductal carcinoma in situ (DCIS). 
Denmark offered a useful real world reference because organized breast cancer screening began in some regions 17 years earlier than in others, allowing researchers to track how breast cancer diagnoses changed immediately after screening was introduced and how those patterns evolved over longer periods. "When screening is introduced, the number of breast cancer diagnoses initially rises because cancers are detected earlier than they would have been without screening. Over time, this should be followed by a drop, as some of these cancers would otherwise have been diagnosed later. 
This pattern can also be affected if women in either group continue to undergo screening after the trials had ended, which was common. If researchers do not take these factors into account, the initial increase can be mistaken for overdiagnosis," says Elsebeth Lynge, professor emerita at Department of Public Health, University of Copenhagen. 
By comparing breast cancer incidence at matching points in time in the randomized trials and in Denmark's routine screening programs, the researchers found that the additional breast cancer cases detected in randomized trials closely resembled patterns seen in Denmark, where overdiagnosis associated with screening is estimated to be below 5%. 
Overdiagnosis occurs when screening detects a breast cancer that would never have become life-threatening or caused symptoms during a woman's lifetime meaning that without screening, the woman would never have known that the cancer was present and the definition can also include women who die from another cause shortly after receiving a breast cancer diagnosis, since screening may have offered little benefit because poor health or limited life expectancy meant that finding and treating the cancer was unlikely to improve health or extend life. 
A key issue is that screening changes when a cancer is diagnosed: when mammography is introduced, more cancers are detected earlier, producing an initial rise in the number of diagnoses, and because some of those cancers would eventually have been found even without screening, diagnosis rates should later decline as those cases shift forward in time if a study ends before enough time has passed for that decline to become visible, researchers may incorrectly interpret some of the early increase as overdiagnosis, and estimates can also be distorted when women in control groups later receive screening themselves. 
The new analysis suggests that accounting for these timing effects can substantially change estimates of how often mammography identifies cancers that would otherwise never have caused a problem. "Taken together, we believe some previous high estimates of overdiagnosis, which influenced screening guidelines and communication, were based on evidence before trial data had fully matured.