Long-term follow-up of randomized trials provide the most accurate estimates of overdiagnosis. Estimates from follow-up of service screening studies are almost as accurate if there is sufficient adjustment for lead time and risk status. When properly analyzed data from both of these types of trials indicate that the rate of overdiagnosis at screening mammography is clinically negligible: 0–5%. Population trend studies are a potentially highly inaccurate means to estimate overdiagnosis. Most cases of DCIS detected at screening are medium and high grade with substantial potential to become an invasive disease. To avoid overtreatment, clinicians need to tailor their treatment of DCIS to the histologic and molecular characteristics of each case.
As the evidence that screening can substantially reduce breast cancer mortality was being confirmed in numerous studies during the past 30 years, the focus of screening controversies shifted from the existence and measurement of benefit to potential “harms” and costs of screening, as well as to proposals to reduce the frequency of screening and to limit the age of women offered screening to those aged 50–70 years or to deny screening to those with no known risk factors. It is sadly ironic that these issues have gained the forefront of media attention, whereas the lifesaving results of screening have been marginalized. Indeed, women should now be aware that breast cancer mortality among screened women aged 40–69 years in the Swedish Two-County Randomized Trial was reduced by 31% among those invited to screening . Randomized trials underestimate the actual benefit from screening due to noncompliance of some study group women and contamination of some control group women. Service screening studies provide higher, more accurate estimates.
Among seven European service screening studies analyzed with incidence-based mortality methods, breast cancer mortality was 25% lower for invited versus not invited women, and 38% lower for screened versus not screened women . Among seven other European service screening studies analyzed using case-control methods, corresponding breast cancer mortality reductions were 31% for invited versus not invited women and 52% for screened versus not screened women .
The purpose of this review article on overdiagnosis, which has recently gained the spotlight as a purported major harm from screening, was to demonstrate that among screen-detected cancers the possibility of overdiagnosis is extremely low, less than 5%. Furthermore, this review article demonstrates that overdiagnosis has less clinical significance than the vastly larger clinical benefits of early detection established in screening studies. It should also be appreciated that more recent improvements in imaging technology such as 2D digital mammography and 3D digital tomosynthesis should allow even greater benefits than shown in the randomized trials and service screening studies .
The concept of overdiagnosis postulates that some breast cancers detected at screening would never be known to the patient or her physician in the absence of screening. It has been alleged that such overdiagnosed breast cancers never produce any clinical signs or symptoms and never represent a cause of death. There is no way to determine by pathologic examination whether an individual cancer has been overdiagnosed. Thus, the existence and frequency of overdiagnosis has only been inferred by mathematical calculation based on trends of breast cancer incidence or on data from screening trials. Yet, such calculations may be grossly misleading if based on basic misassumptions or improper flawed techniques such as insufficient follow-up or failure to correct for risk factors in the populations . If overdiagnosis does actually occur in the real world, women with overdiagnosed cancers would receive “unnecessary” treatments such as lumpectomy, mastectomy, chemotherapy, and radiation therapy. Additionally, these women would experience the unnecessary anxiety of knowing that they have breast cancer. These women and their families, employers, and medical insurance providers would incur “needless” costs for the consequent diagnostic and therapeutic procedures. Thus, if existent, overdiagnosis would represent harm from screening. The frequency of overdiagnosis would determine whether this harm is trivial or substantial when weighed against the benefits from early detection of breast cancer. Overdiagnosis is completely different from a “false-positive biopsy,” which is an abnormality that is biopsied on the basis of suspicious imaging findings and subsequently found to be benign on examination of the biopsy specimen.
The frequency of overdiagnosis has been estimated on the basis of data from randomized screening trials, service screening studies, changes and trends in incidence, and stages of cancer in populations. Analytic methods applied to these databases differ substantially in their accuracy and their conclusions. Accurate estimates indicate that the frequency of overdiagnosis is extremely low. Between 0% and 5% of screen-detected cancers are overdiagnosed . Inaccurate estimates have led to the erroneous conclusion that as many as 30% of breast cancers are being overdiagnosed. It is understandable that many women may feel confused and frightened and consequently deterred from being screened, and some physicians may be dissuaded from advising screening for their patients. To clarify the controversy, this review article demonstrates why the risk of overdiagnosis has been greatly exaggerated and that the risk is negligible or nonexistent compared to the substantial benefits from screening.
Why estimation of overdiagnosis by means of trend studies is unreliable and inaccurate
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Accurate estimation of overdiagnosis using service screening requires sufficient adjustment for detection lead time and risk status
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Long-term follow-up of randomized trials provides the most accurate estimates of overdiagnosis
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Other evidence that most cases of screen-detected ductal carcinoma in situ do not represent overdiagnosis
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Discussion
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