Overdiagnosis refers to the detection of cancers that would never come to light in a patient’s lifetime and are only identified by means of screening. Exactly how much overdiagnosis currently exists with screening mammography is uncertain. Because we do not know for certain which tumors would ultimately lead to death if left untreated and which would not, we cannot directly measure overdiagnosis and how best to estimate it is a matter of controversy. A conservative estimate of overdiagnosis with mammography would be on the order of 10%, but estimates have ranged as high as 54%. We know from multiple studies that ultrasound (US) screening mostly detects small, invasive, node-negative cancers; and in the ACRIN 6666 study, there was a greater tendency for US-only–detected tumors to be low grade than those detected with mammography. However, the population of patients undergoing screening US can be expected to differ from the average screening mammography population in that they will have higher breast density, they will be younger, and they may also have higher breast cancer risk than the population undergoing screening mammography. These factors may be associated with more aggressive tumors. There is no way to know whether we will be increasing overdiagnosis without performing a large randomized controlled study with very long-term follow-up. Even if some cancers are overdiagnosed with US, there will be a greater proportion of lethal breast cancers that are successfully treated because of screening US. The more important task is to learn how to correctly diagnose and appropriately treat nonlethal cancers.
In 2012, the New England Journal of Medicine published an article by Bleyer and Welch claiming that 31% of all breast cancers are “overdiagnosed” and that screening mammography has only a “small effect” on breast cancer mortality, opening the door to yet another heated debate over the benefit of screening mammography. Ironically, this new debate comes at a time when the medical community is faced with the prospect of an expansion of breast cancer screening in the form of whole-breast screening ultrasound (US) for women with dense breasts. The question that naturally follows is would there be an ultimate benefit from US? Or would it only result in needless cancer treatment?
Stemming from the efforts of a breast cancer patient in Connecticut whose tumor was occult on mammography and diagnosed only after US, in 2009, Connecticut became the first state to pass legislation requiring that breast density be included in the mammography report and brought the issue of breast density and mammographic sensitivity into the public limelight. At this time, over half of the states have followed suite and either passed or introduced legislation requiring breast density reporting. Similar legislation has also been introduced at the federal level. The laws are intended to make women aware of the limitations of mammography in dense breasts and to open up dialogue between women and their physicians regarding other supplemental screening options which include whole-breast US, magnetic resonance imaging (MRI), and digital breast tomosynthesis. The exact nature of the supplemental screening is not specified in the legislation, but the expectation is that the most women will seek US screening as it is less expensive and in general better tolerated than MRI. This is despite the continued recommendation by the American College of Radiology that only those at high risk for breast cancer (lifetime risk >20%) undergo supplementary screening and that supplementary screening should be performed with MRI rather than US, with US reserved for those high-risk women who cannot undergo MRI .
What is the true extent of overdiagnosis with screening mammography alone?
Overdiagnosis refers to the detection of cancers that would never come to light in a patient’s lifetime and are only identified by means of screening. Therefore, a patient undergoes treatment with its associated harms but never derives the benefit of additional life years gained. Overdiagnosis is not unique to breast cancer and is also implicated in other cancers, including lung, thyroid, and renal cancers. These “overdiagnosed” cancers are presumably small, slow-growing, nonpalpable tumors which lend themselves to detection with yearly screening, probably more so by repeated opportunities for detection than by imaging conspicuity. Proponents of overdiagnosis cite two factors in support of their argument : First, although there has been a significant increase in breast cancer incidence over the past 20 years, there has been no significant increase in mortality, and the observed decrease in mortality can be explained by better treatment alone. Second, there has been no significant change in the rate of diagnosis of late-stage cancers. In fact, according to Bleyer and Welch , the much greater absolute reduction in breast cancer mortality (20 per 100,000) compared to the reduction in the number of late-stage cancers (8 per 100,000) means that the effect of screening mammography is small.
Although most experts agree that overdiagnosis exists, its extent is a matter of great debate. Because there is no way to tell exactly which cancers would never go on to be life threatening, the rate of cancer overdiagnosis has to be estimated indirectly from large-scale breast cancer screening and epidemiologic studies.
The existence of overdiagnosis can be demonstrated by comparing the incidence in a screened to a nonscreened population. Assuming variables such as age and breast cancer risk are the same between the two populations, the cumulative incidence of breasts cancer should be the same between the two populations. If there is a difference in the cancer incidence in the two groups, it must be that the excess numbers (which usually occurs in the screened group) come from nonclinically important cancers in the screened group that were detected only because of screening and never would have surfaced clinically. Presumably, this excess number of cancers also exists in the control group but has not been detected, or as Zahl suggests, may have spontaneously regressed.
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Does more imaging necessarily mean more overdiagnosis?
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Are there features of the patient population that would be screened that may lead to a high incidence of more aggressive cancers?
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By adding screening US, are we likely to increase the rate of overdiagnosis?
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References
1. Bleyer A., Welch H.G.: Effect of three decades of screening mammography on breast cancer incidence. N Engl J Med 2012; 367: pp. 1998-2005.
2. Price E.R., Hargreaves J., Lipson J.A., et. al.: The California breast density information group: a collaborative response to the issues of breast density, breast cancer risk, and breast density notification legislation. Radiology 2013; 269: pp. 887-892.
3. Ceugnart L., Deghaye M., Vennin P., et. al.: Organized breast screening: answers to recurring controversies. Diagn Interv Imaging 2014; 95: pp. 355-359.
4. Zahl P.H., Maehlen J., Welch H.G.: The natural history of invasive breast cancers detected by screening mammography. Arch Intern Med 2008; 168: pp. 2311-2316.
5. Duffy S.W., Parmar D.: Overdiagnosis in breast cancer screening: the importance of length of observation period and lead time. Breast Cancer Res 2013; 15: pp. R41.
6. Independent UK Panel on Breast Cancer Screening: The benefits and harms of breast cancer screening: an independent review. Lancet 2012; 380: pp. 1778-1786.
7. Puliti D., Duffy S.W., Miccinesi G., et. al., EUROSCREEN Working Group: Overdiagnosis in mammographic screening for breast cancer in Europe: a literature review. J Med Screen 2012; 19: pp. 42-56.
8. Jørgensen K.J., Gøtzsche P.C.: Overdiagnosis in publicly organised mammography screening programmes: systematic review of incidence trends. BMJ 2009; 339: pp. b2587.
9. Kopans D.B., Smith R.A., Duffy S.W.: Mammographic screening and “overdiagnosis”. Radiology 2011; 260: pp. 616-620.
10. Feig S.A.: Pitfalls in accurate estimation of overdiagnosis: implications for screening policy and compliance. Breast Cancer Res 2013; 15: pp. 105.
11. Kopans D.B.: Point: The New England Journal of Medicine article suggesting overdiagnosis from mammography screening is scientifically incorrect and should be withdrawn. J Am Coll Radiol 2013; 10: pp. 317-319.
12. Merry G.M., Mendelson E.B.: Update on screening breast ultrasonography. Radiol Clin North Am 2014; 52: pp. 527-537.
13. Berg W.A., Zhang Z., Lehrer D., et. al., ACRIN 6666 Investigators: Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast cancer risk. JAMA 2012; 307: pp. 1394-1404.
14. Parris T., Wakefield D., Frimmer H.: Real world performance of screening breast ultrasound following enactment of Connecticut Bill 458. Breast J 2013; 19: pp. 64-70.
15. Hooley R.J., Greenberg K.L., Stackhouse R.M., et. al.: Screening US in patients with mammographically dense breasts: initial experience with Connecticut Public Act 09-41. Radiology 2012; 265: pp. 59-69.
16. Rauch G.M., Kuerer H.M., Scoggins M.E., et. al.: Clinicopathologic, mammographic, and sonographic features in 1,187 patients with pure ductal carcinoma in situ of the breast by estrogen receptor status. Breast Cancer Res Treat 2013; 139: pp. 639-647.
17. Wang L.C., Sullivan M., Du H., et. al.: US appearance of ductal carcinoma in situ. Radiographics 2013; 33: pp. 213-228.
18. Corsetti V., Houssami N., Ferrari A., et. al.: Breast screening with ultrasound in women with mammography-negative dense breasts: evidence on incremental cancer detection and false positives, and associated cost. Eur J Cancer 2008; 44: pp. 539-544.
19. Kelly K.M., Dean J., Lee S.J., et. al.: Breast cancer detection: radiologists’ performance using mammography with and without automated whole-breast ultrasound. Eur Radiol 2010; 20: pp. 2557-2564.
20. Chang J.C., Hilsenbeck S.G.: Prognostic and predictive markers.Harris J.R.Lippman M.E.Morrow M. et. al.Diseases of the breast.2010.Lippincitt Williams & WilkinsPhiladelphia PA:pp. 443-457.
21. Corsetti V., Houssami N., Ghirardi M., et. al.: Evidence of the effect of adjunct ultrasound screening in women with mammography-negative dense breasts: interval breast cancers at 1 year follow-up. Eur J Cancer 2011; 47: pp. 1021-1026.
22. Chae E.Y., Kim H.H., Cha J.H., et. al.: Evaluation of screening whole-breast sonography as a supplemental tool in conjunction with mammography in women with dense breasts. J Ultrasound Med 2013; 32: pp. 1573-1578.
23. Ho J.M., Jafferjee N., Covarrubias G.M., et. al.: Dense breasts: a review of reporting legislation and available supplemental screening options. AJR Am J Roentgenol 2014; 203: pp. 449-456.
24. D’Orsi C.J., Sickles E.A.: To seek perfection or not? That is the question. Radiology 2012; 265: pp. 9-11.
25. Liebens F.P., Carly B., Pastijn A., et. al.: Management of BRCA1/2 associated breast cancer: a systematic qualitative review of the state of knowledge in 2006. Eur J Cancer 2007; 43: pp. 238-257.
26. Eriksson L., Czene K., Rosenberg L., et. al.: The influence of mammographic density on breast tumor characteristics. Breast Cancer Res Treat 2012; 134: pp. 859-866.
27. Yaghjyan L., Colditz G.A., Collins L.C., et. al.: Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to tumor characteristics. J Natl Cancer Inst 2011; 103: pp. 1179-1189.
28. Wang A.T., Vachon C.M., Brandt K.R., et. al.: Breast density and breast cancer risk: a practical review. Mayo Clin Proc 2014; 89: pp. 548-557.
29. Partridge A.H., Goldhirsch A., Gelber S., et. al.: Breast cancer in younger women.Harris J.R.Lippman M.E.Morrow M. et. al.Diseases of the breast.2010.Lippincitt Williams & WilkinsPhiladelphia PA:pp. 1073-1082.
30. Gur D., Sumkin J.H.: Screening for early detection of breast cancer: overdiagnosis versus suboptimal patient management. Radiology 2013; 268: pp. 327-328.