Frequency of incidental breast cancer and precancerous lesions in autopsy studies: a systematic review and meta-analysis, 2017.
The burden of occult cancer, 2026
December 14, 2017 https://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3808-1
This study about frequency of incidental breast cancer lesions in autopsies reinforces the fear that among the women treated after detection of a cancerous lesion through screening, and therefore in absence of symptoms, a certain number (one out of two in the Autier study from the Netherlands) would never have suffered from it during their lifetime; the removal of a breast, unnecessary radiotherapy or tiring chemotherapy could have been avoided for these women.
Authors : Elizabeth T. Thomas1 , Chris Del Mar 2 , Paul Glasziou 2 , Gordon Wright 1 , Alexandra Barratt 3 and Katy J. L. Bell 2,3
1 Faculty of Health Sciences and Medicine, Bond University, Robina, QLD 4229, Australia.
2 Centre for Research in Evidence-based Practice, Faculty of Health Sciences and Medicine, Bond University, Robina, QLD 4229, Australia.
3 Sydney School of Public Health, Sydney Medical School, Edward Ford Building (A27), University of Sydney, Fisher Road, Sydney, NSW 2006, Australia
Background
Autopsy studies have demonstrated the frequency of occult cancers in the population, but the evaluations performed by these primary studies involved a small number of deceased patients each time.
Results
The authors included 13 studies from 10 different countries, over 6 decades (from 1948 to 2010), comprising 2363 autopsies with 99 cases of so-called “incidentalomas” (cancers of incidental finding), or precancerous lesions.
When the histological examination was more comprehensive (on more than 20 histological sections), there were more incidentalomas detected, mostly in situ cancers and atypical hyperplasias, but few invasive cancers.
This means that the more histological research is carried out on deceased persons, the more latent cancers are found, with an average frequency of this “accidental” cancer of around 19.5% (0.85% invasive cancer + 8.9% in situ cancer + 9.8% atypical hyperplasia).
Therefore, the more we seek and the more we find, which raises questions about the development of more and more efficient investigative techniques that are going to discover more and more of these lesions abusively. The consequences of the resulting over-treatments are to be considered even more seriously in older women because of the increased susceptibility to adverse effects of treatments in this population.
Conclusion
Systematic review in ten countries over more than six decades has found that incidental discovery of occult, in situ cancers or precancerous lesions is very common in women, in whom breast disease was not known during their lifetime.
It appears that cancerous or pre-cancerous lesions are discovered incidentally in 2 out of 10 women during these autopsies. The authors estimate that 40% of invasive cancers detected by systematic mammography and 24% of all invasive cancers would be over-diagnosed.
This high frequency of undetected cancers, in situ and atypical hyperplasias in these autopsy studies, suggests that screening programs should be more cautious in promoting detection methods with increased sensitivity, thus increasing these unnecessary diagnoses.
What is the burden of occult cancer in the population?
This question is addressed by a study based on autopsies conducted over a 66-year period in Japan, published in the JAMA Network on February 5, 2026.
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2844664#250786366
This study seeks to determine how the hidden burden of cancer has evolved in Japan over a 66-year period by examining data from nationwide autopsies of people who died from causes other than cancer.
As we know from the systematic review of autopsy studies presented above, and from Nielsen’s autopsy studies (see reference at the bottom of the article) many years ago, a number of cancers are not diagnosed during the patient’s lifetime, and patients die with undiagnosed cancer, but not from it. This series of studies has shown that there is a significant reservoir of occult cancers, far greater than suggested by the registers of diagnosed cancers.
For example, in the case of breast cancer, one study showed that the rate of tumours found in the breasts of women who died from other causes was four times higher than that of the living population at the same time, based on 686 women who underwent autopsies. (Nielsen, see references at the bottom of the article)
The Japanese study covers 1.5 million autopsies. It is a retrospective cohort study based on an autopsy registry that lists 1,486,557 autopsies performed over 66 years, i.e., between 1958 and 2023.
What are the results?
Over the entire period, 55.2% of autopsies revealed at least one cancer, a proportion that rose from less than 40% in the 1960s to around 60% in the late 1980s, then stabilised above 50%. Multiple primary cancers increased significantly, from 1.8% of autopsies in 1974 to 14.4% in 2023.
This shows that the hidden burden of cancer is not negligible and can vary according to historical periods, the intensity of screening to which the population is subjected, diagnostic methods, and access to care.
Traditional registries underestimate the true frequency of cancers. The excess cancers primarily concern prostate cancer and thyroid cancer.
For occult prostate cancer, the prevalence (number of cases of a disease in a population at a given time, including both new and old cases) was 6.9 times higher than the number of clinical cases at the same time in the living population.
For thyroid cancer, the situation is even worse, with prevalence rates approximately 95 times higher in women and 61 times higher in men compared to the number of clinical cases present in the living population at the same time.
A small percentage of these occult cancers were even already metastatic, for example, in the case of lung cancer, pancreatic cancer, bile duct cancer, and haematological malignancies (blood cancers).
These data further confirm that there is a significant reservoir of occult cancers, sometimes even metastatic, in the population. Overdiagnosis is once again at the heart of the problem, generated by screening that favours the detection of cancers that would never have manifested themselves and would never have threatened life.
This prompts reflection on the relevance of more targeted screening, say the authors, to isolate those most at risk and detect truly threatening tumours, those that will become truly significant, in order to avoid these cases of overdiagnosis.
The overdiagnosis of cancer, which is greatly underestimated, has significant consequences for patients, unnecessarily placing them on a path to illness.
Conclusion
This analysis provides a better understanding of the actual prevalence of cancer in a population, thanks to the autopsies performed.
The authors conclude: “This cohort study of autopsies across Japan found a substantial reservoir of undiagnosed cancer, including some with metastatic potential. These findings highlight the persistent value of autopsy for assessing cancer burden and underscore the need to refine approaches for early detection while minimizing overdiagnosis.”
Autopsy studies will refine our understanding of the natural history of cancers, but also shift the focus of the fight against cancer away from mass screening, which greatly encourages unnecessary diagnoses by detecting lesions that would never have manifested themselves.
Research can also be directed towards biological markers to distinguish between indolent lesions and those that have real potential to develop and threaten the patient’s life, in order to avoid overtreatment, which is very costly in terms of people’s health and healthcare resources.
Reference
110 systematic autopsies (Nielsen study, Denmark, 1987)
Mammography and pathological examination of the breasts of women aged 20 to 54 with no history of breast disease show:
20% malignant lesions, including 2% invasive,
7% atypical hyperplasia,
37% breast cancers between the ages of 40 and 54,
39% breast cancers between the ages of 40 and 49.
Nielsen M, Jensen J, Andersen J. Precancerous and Cancerous Breast Lesions During Lifetime and at Autopsy. A Study of 83 Women. Cancer 1984; 54: 612-615.
Nielsen M, Thomsen JL, Primdahls et al. Breast cancer and atypia among young and middle-aged women: a study of 110 medicolegal autopsies. Br J Cancer 1987; 56: 814-819.
Autopsy studies published between 1984 and 1987: 686 women who died from causes other than breast cancer were autopsied. Twenty-two invasive cancers were found, or 32 per thousand, which is four times higher than the rate calculated from cases diagnosed in clinical practice during the same period.
The pool of histological cancer diagnoses is immense. ‘The more we look, the more histological abnormalities we find.’
‘Overdiagnosis: Making People Sick in the Pursuit of Health’ Welch HG et al., Beacon Press, Boston 2011; Prescrire Prize 2012
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