Overdiagnosed disease is a neoplasm that would never become clinically apparent prior to a patient's death without screening. An example is a tumor that is found by mammographic screening that would never be evident otherwise.
Autopsy studies have found tumors in people who died of causes unrelated to the tumors. The studies indicate that lesions exist that fulfill the histologic criteria of cancer but that were not clinically apparent in the woman's lifetime. An overview of seven autopsy studies documents a median prevalence of 1.3% for undiagnosed invasive breast cancer (range, 0%-1.8%) and 8.9% for undiagnosed ductal carcinomain situ (range, 0%-14.7%).[16,17] Finding such cancers by mammography would be overdiagnosis. Because cancers that will progress cannot be distinguished with certainty from those that will not, these tumors are often treated (with surgery and possibly with radiation, chemotherapy, and hormonal therapy). This treatment would constitute overtreatment because it would not confer a benefit to the woman.
It is difficult to determine the proportion of screen-detected cancers that are overdiagnosed. A widely accepted estimation method is to compare breast cancer incidence over time in a screened population with that of an unscreened population. Randomized screening trials are the most credible, but the period of screening versus control is limited in all the trials. If a woman complies with not being screened during the study period but gets screened afterwards, then a breast cancer that would have been found had the woman been assigned to screening would likely be found shortly thereafter. (Most of the women in the control group in the Swedish trials were assigned to receive a control mammogram at the end of the study period.) Such delayed screening will also find overdiagnosed cancers; the cumulative incidence of cancers will be similar in the two groups, irrespective of the magnitude of overdiagnosis.
Population-based studies suffer from the same problem as randomized trials, although to a lesser extent. However, the population-based studies have their own problems. Unbiased estimates would only be possible if the screened and nonscreened populations were the same except for screening, but the populations may differ in time, in geography, in culture, and by the use of postmenopausal hormone therapy. In addition, investigators differ in their assessments of overdiagnosis regarding how and whether to adjust for characteristics such as lead-time bias.[18,19] As a consequence, the magnitude of overdiagnosis due to mammographic screening is controversial, with estimates ranging from 7% to 50%.[18,19,20,21]
Several observational population-based comparisons consider breast cancer incidence before and after adoption of screening.[22,23,24,25,26] If there were no overdiagnosis-and other aspects of screening were unchanged-there would be a rise in incidence followed by a decrease to below the prescreening level, and the cumulative incidence would be similar. Such results have not been observed. Breast cancer incidence rates increase at the initiation of screening without a compensatory drop in later years. For example, in Sweden, the age-specific incidence rates doubled between 1986 and 2002 for all age groups participating in screening. Another study in 11 rural Swedish counties showed a persistent increase in breast cancer incidence following the advent of screening. A population-based study from Norway and Sweden showed increases in invasive breast cancer incidence of 54% in Norway and 45% in Sweden in women aged 50 to 69 years, following the introduction of nationwide screening programs. No corresponding decline in incidence in women older than age 69 years was ever seen. Similar findings suggestive of overdiagnosis have been reported from the United Kingdom  and the United States.[25,26]
- Kerlikowske K, Grady D, Barclay J, et al.: Positive predictive value of screening mammography by age and family history of breast cancer. JAMA 270 (20): 2444-50, 1993.
- Elmore JG, Barton MB, Moceri VM, et al.: Ten-year risk of false positive screening mammograms and clinical breast examinations. N Engl J Med 338 (16): 1089-96, 1998.
- Christiansen CL, Wang F, Barton MB, et al.: Predicting the cumulative risk of false-positive mammograms. J Natl Cancer Inst 92 (20): 1657-66, 2000.
- Welch HG, Fisher ES: Diagnostic testing following screening mammography in the elderly. J Natl Cancer Inst 90 (18): 1389-92, 1998.
- Rosen EL, Baker JA, Soo MS: Malignant lesions initially subjected to short-term mammographic follow-up. Radiology 223 (1): 221-8, 2002.
- Feig SA, Ehrlich SM: Estimation of radiation risk from screening mammography: recent trends and comparison with expected benefits. Radiology 174 (3 Pt 1): 638-47, 1990.
- Helzlsouer KJ, Harris EL, Parshad R, et al.: Familial clustering of breast cancer: possible interaction between DNA repair proficiency and radiation exposure in the development of breast cancer. Int J Cancer 64 (1): 14-7, 1995.
- Swift M, Morrell D, Massey RB, et al.: Incidence of cancer in 161 families affected by ataxia-telangiectasia. N Engl J Med 325 (26): 1831-6, 1991.
- Kopans DB: Mammography and radiation risk. In: Janower ML, Linton OW, eds.: Radiation Risk: a Primer. Reston, Va: American College of Radiology, 1996, pp 21-22.
- Suleiman OH, Spelic DC, McCrohan JL, et al.: Mammography in the 1990s: the United States and Canada. Radiology 210 (2): 345-51, 1999.
- Lerman C, Trock B, Rimer BK, et al.: Psychological side effects of breast cancer screening. Health Psychol 10 (4): 259-67, 1991.
- Gram IT, Lund E, Slenker SE: Quality of life following a false positive mammogram. Br J Cancer 62 (6): 1018-22, 1990.
- Burman ML, Taplin SH, Herta DF, et al.: Effect of false-positive mammograms on interval breast cancer screening in a health maintenance organization. Ann Intern Med 131 (1): 1-6, 1999.
- Pisano ED, Earp J, Schell M, et al.: Screening behavior of women after a false-positive mammogram. Radiology 208 (1): 245-9, 1998.
- Brewer NT, Salz T, Lillie SE: Systematic review: the long-term effects of false-positive mammograms. Ann Intern Med 146 (7): 502-10, 2007.
- Welch HG, Black WC: Using autopsy series to estimate the disease "reservoir" for ductal carcinoma in situ of the breast: how much more breast cancer can we find? Ann Intern Med 127 (11): 1023-8, 1997.
- Black WC, Welch HG: Advances in diagnostic imaging and overestimations of disease prevalence and the benefits of therapy. N Engl J Med 328 (17): 1237-43, 1993.
- Duffy SW, Lynge E, Jonsson H, et al.: Complexities in the estimation of overdiagnosis in breast cancer screening. Br J Cancer 99 (7): 1176-8, 2008.
- Gøtzsche PC, Jørgensen KJ, Maehlen J, et al.: Estimation of lead time and overdiagnosis in breast cancer screening. Br J Cancer 100 (1): 219; author reply 220, 2009.
- Gøtzsche PC, Nielsen M: Screening for breast cancer with mammography. Cochrane Database Syst Rev (4): CD001877, 2006.
- Zackrisson S, Andersson I, Janzon L, et al.: Rate of over-diagnosis of breast cancer 15 years after end of Malmö mammographic screening trial: follow-up study. BMJ 332 (7543): 689-92, 2006.
- Hemminki K, Rawal R, Bermejo JL: Mammographic screening is dramatically changing age-incidence data for breast cancer. J Clin Oncol 22 (22): 4652-3, 2004.
- Jonsson H, Johansson R, Lenner P: Increased incidence of invasive breast cancer after the introduction of service screening with mammography in Sweden. Int J Cancer 117 (5): 842-7, 2005.
- Johnson A, Shekhdar J: Breast cancer incidence: what do the figures mean? J Eval Clin Pract 11 (1): 27-31, 2005.
- White E, Lee CY, Kristal AR: Evaluation of the increase in breast cancer incidence in relation to mammography use. J Natl Cancer Inst 82 (19): 1546-52, 1990.
- Feuer EJ, Wun LM: How much of the recent rise in breast cancer incidence can be explained by increases in mammography utilization? A dynamic population model approach. Am J Epidemiol 136 (12): 1423-36, 1992.
- Zahl PH, Strand BH, Maehlen J: Incidence of breast cancer in Norway and Sweden during introduction of nationwide screening: prospective cohort study. BMJ 328 (7445): 921-4, 2004.