For decades, women have been told that breast cancer screening comes with a hefty catch: overdiagnosis, the detection of cancers that would never have caused symptoms or threatened a woman's health during her lifetime. Estimates from randomized trials have ranged wildly, with some studies suggesting that 30-50% of breast cancers found through screening fall into this harmless-but-terrifying category. Those numbers have shaped international guidelines and countless anxious conversations.
Turns out those scary figures may have been an artifact of impatience. A new study led by researchers at the University of Southern Denmark and Lillebælt Hospital, published via ScienceDaily, reanalyzed all eight randomized trials of mammography screening and compared them with real-world data from Denmark. Their conclusion: overdiagnosis is likely below 5%, not the 30-50% that has haunted screening debates for years.
"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 the University of Southern Denmark and Lillebælt Hospital. "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."
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%. Denmark made a useful reference because organized screening began in some regions 17 years earlier than in others, allowing researchers to track how diagnoses changed immediately after screening was introduced and how those patterns evolved over time.
"When screening is introduced, the number of breast cancer diagnoses initially rises because cancers are detected earlier than they would have been without screening," explains Elsebeth Lynge, professor emerita at the Department of Public Health, University of Copenhagen. "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."
The team compared breast cancer incidence at matching points in time in the randomized trials and in Denmark's routine screening programs. This allowed them to assess whether the patterns were similar and what those similarities might reveal about the true scale of overdiagnosis.
"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," says Matejka Rebolj, Senior Epidemiologist at Queen Mary University of London. "When interpreted in their full temporal context, randomized trial data are consistent with overdiagnosis of less than five percent, rather than with estimates nearing 50%."
Overdiagnosis occurs when screening detects a breast cancer that would never have become life-threatening or caused symptoms during a woman's lifetime. Without screening, the woman would never have known that the cancer was present. The definition can also include women who die from another cause shortly after receiving a breast cancer diagnosis. In these cases, 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.
The 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. Some of those cancers would eventually have been found even without screening, meaning 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. 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. Understanding both the benefits and potential downsides of screening is important for women deciding whether to participate in breast cancer screening programs.
"Most women will not develop breast cancer, but with this study we can now be reassured that the benefits of detecting breast cancer early and preventing premature death will outweigh the small risk of unnecessary treatment," says Sisse Helle Njor. "With this in mind, we hope this study will provide a framework for a more realistic interpretation of the evidence and help us better inform women when they are invited for screening."
The researchers performed a new analysis of existing mammography screening research. Their analysis included all eight randomized trials in this field: the New York Health Insurance Plan, Malmö, Two-County, Edinburgh, the Canadian National Breast Screening Study, Stockholm, Gothenburg, and UK Age. Two regional screening programs in Denmark were used as a reference. The researchers examined both invasive breast cancer and ductal carcinoma in situ (DCIS).
When reassessing the earlier trials, the team focused on three factors that can influence estimates of overdiagnosis. After taking these differences in screening exposure and follow-up into account, the researchers concluded that overdiagnosis may be substantially less common than earlier estimates suggested.
Casper Urth Pedersen is supported by the Novo Nordisk Foundation (reference: NNF22OC0076184), and Matejka Rebolj is supported by Cancer Research UK (reference: C8162/A29083).
Materials provided by University of Southern Denmark Faculty of Health Sciences. Note: Content may be edited for style and length.