A A
Revised & updated
Published

This position statement has been endorsed by the Australian Health Ministers’ Advisory Council Standing Committee on Screening, Cancer Council Australia and the Royal Australian and New Zealand College of Radiologists, and is supported by the Cancer Australia Advisory Council.

Context

National Breast and Ovarian Cancer Centre* first released a position statement on overdiagnosis from mammographic screening in 2008, followed by an update in 2010. The present statement is a further update by Cancer Australia. This update was based on a review of the published scientific literature and incorporation of input from international and national experts in the field.

Cancer Australia position statements address significant clinical issues, emerging issues in cancer control and issues of ongoing interest, using the best available evidence. The purpose of this position statement is to provide evidence-based information on overdiagnosis from population-based mammographic screening for breast cancer. The intended audiences are cancer organisations, health professionals, medical colleges, media, and policy makers.

Definition

“Overdiagnosis” from breast screening does not refer to error or misdiagnosis, but rather refers to breast cancer diagnosed by screening that would not otherwise have been diagnosed during a woman’s lifetime. “Overdiagnosis” includes all instances where cancers detected through screening (ductal carcinoma in situ or invasive breast cancer) might never have progressed to become symptomatic during a woman’s life, i.e., cancer that would not have been detected in the absence of screening.1 It is not possible to precisely predict at diagnosis, to which cancers overdiagnosis would apply.

Summary

  • Cancer Australia supports the importance of mammographic screening in reducing breast cancer mortality.
  • The national BreastScreen Australia Evaluation indicated a reduction in breast cancer mortality for the age group of 50-69 years of approximately 21-28% at the participation level of 56%.
  • Participation in the BreastScreen Australia Program would result in around 8 deaths prevented for every 1000 women screened every two years from age 50 to age 74.
  • A majority of breast cancers found through screening would be progressive and would become symptomatic within a woman’s lifetime if left untreated.
  • It is likely that some screen-detected breast cancers (ductal carcinoma in situ or invasive breast cancer) might never have progressed to become symptomatic in a woman’s lifetime. Detection of these cancers is sometimes referred to as “overdiagnosis”.
  • It is not possible to precisely predict at diagnosis, to which cancers overdiagnosis would apply.
  • Estimates of overdiagnosis vary widely. Based on UK and European reviews, it is estimated that for every 1000 women in Australia who are screened every two years from age 50 to age 74, around 8 (between 2 and 21) breast cancers may be found and treated that would not have been found in a woman’s lifetime.
  • Research is needed, including molecular and genomic research, to find means of identifying cancers that would be of minimal risk of progression and therefore could be managed more conservatively.
  • Information about the benefits of mammographic screening as well as the risks, including overdiagnosis, can assist women to make informed decisions about screening participation.

Evidence for mammographic screening

Mammographic screening has been shown from randomised trials to reduce death rates from breast cancer.1-12 In 2002, the reduction was estimated by an Expert Group of the International Agency for Research on Cancer (IARC) to approximate 35% in 50-69 year old women who participated in regular screening.1 Since then, for screening participants of all ages, lower breast cancer reduction (25%) was estimated in a meta-analysis of trial data.13 From trial data for women invited to screening compared with women not invited, reductions of around 20% were estimated.13-15

Evaluation of mammographic screening from observational studies in Australia has provided broadly consistent results that point to a higher reduction in breast cancer mortality in percentage terms from screening participation, than in the randomised trials. Studies from South Australia17 and Western Australia18 of screening participants compared to non-participants indicated a reduction in breast cancer mortality for 50-69 years ranging from 47-52%. A population study from New South Wales indicated a breast cancer mortality reduction for 50-69 years of 32% for a 70% participation rate.16  The national BreastScreen Australia Evaluation indicated a reduction in breast cancer mortality at a population level for the target age group of 50–69 years of approximately 21-28% at the participation level of 56%.19,20 Based on these studies, it is estimated that about 8 deaths would be prevented per 1000 women screened from age 50 through to 74 years, with the estimate ranging with the data source from 6 to10.16-20

Collective results from other countries are also broadly consistent with the 35% reduction estimated by the IARC Expert Group for screening participants in trials,1 although with individual results varying from little or no benefit to reductions of up to 76%.21-43

A recent review of screening service evaluations in Europe presented similar findings to the Australian results, indicating breast cancer mortality reductions in screening participants that were higher than estimated from the trial data.16-20,22,32,33,38,43

The higher reduction in breast cancer mortality from observational studies than that estimated from randomised trial data may reflect advances in screening technology, but it is also probable that estimates were affected by self-selection to screening.  Self-selection to screening may have resulted in an uneven distribution between screened and unscreened women, e.g., due to positive family histories of breast cancer, use of hormone replacement therapy, history of benign breast disease and other risk factors.

There has been international debate and differing conclusions about the contributions of screening and improvements in treatment to reductions over time in breast cancer mortality. One recent analysis interpreted breast cancer mortality trends by age to indicate that these reductions were mostly a result of treatment rather than screening.44 However, statistical modelling analyses of national US data, using seven independent statistical models, gave a combined estimate that around half the mortality reduction was attributable to screening and half to treatment.45 Analysis of data from one region in the UK provided similar estimates.46

Mammographic screening and overdiagnosis

Mammographic screening reduces numbers of breast cancer deaths by bringing forward the date of diagnosis of breast cancers to improve outcomes and reduce mortality. However, some breast cancers detected through screening might never have progressed to become symptomatic during a woman’s lifetime,1 a consequence of which would be overdiagnosis and potentially overtreatment. Examples would include women with screen-detected cancers who die prematurely from accidents or other acute events, or from heart disease or other chronic diseases. In addition, there would be screen-detected cancers that may not progress for many years because of their biology.1,25,42,47,48 Rarely, cancers might regress without treatment, if left, although this would generally be regarded as an unlikely event.25,47,49,50

Overdiagnosis is a statistical inference at the population level. Such inferences have a measure of uncertainty and can vary substantially, depending on underlying statistical assumptions and choice of research design.1,14 Overdiagnosis is not a visually identifiable clinical entity at the individual level. It is not possible to precisely predict at diagnosis, to which cancers overdiagnosis would apply. Therefore, the challenge for ongoing research is not whether the diagnosis is cancer, but whether we can identify which cancers may not require treatment.

Estimates of overdiagnosis

Differences in study design, methodology and assumptions bring different strengths and weaknesses that are open to debate and result in estimates of overdiagnosis that differ widely.

Researchers have interpreted data from the original mammographic screening trials differently,51-58 with estimates of overdiagnosis varying widely.13,48,58-68  Estimates of overdiagnosis also come from studies outside trial settings and from simulation studies.46,69-113 Estimates from these sources also vary widely, depending on methodology and research assumptions, from near zero to as high as one lesion in every three.46,69-113

Reasons why overdiagnosis estimates vary widely include:18,59,61,85,100

  • whether ductal carcinoma in situ (DCIS) is included with invasive breast cancer in the calculations;
  • study design, whether randomised trial, observational study or modelling study;
  • whether results apply to populations offered breast screening or only to individual women invited to breast screening, screening participants, regular screening participants or just screen-detected lesions;
  • the age range of women screened and whether account is taken of any changes in incidence, independent of screening;
  • whether adjustments are made for differences in breast cancer risk factors between screened and unscreened women and what estimates are used when making these adjustments;
  • the duration for which women are followed after screening cessation;
  • the estimates used for lead-time effects (i.e., the time diagnosis was brought forward through screening);
  • whether account is taken of non-diagnostic mammography outside the screening program and how this is done;
  • death rates from other diseases and hence variations in life expectancy at time of screening;
  • screening quality; different screening policies and protocols, including policies for recall for assessment of women with screen-detected abnormalities, and extent of adherence of practice to these different policies.

While a range of 5-13% of all breast carcinomas (invasive and DCIS) was cited as a plausible estimate of extent of overdiagnosis in the first position statement of the former National Breast and Ovarian Cancer Centre, research publications since then have presented widely divergent estimates. Recent modelling studies confirm earlier results that higher levels of overdiagnosis would apply to DCIS than invasive breast cancers.74,101,113 A review of over 50 individual studies, reviews and evidence commentaries cited since 2010, indicated overdiagnosis estimates ranging from near zero to 35% of diagnosed lesions (invasive and DCIS). While the median figure was in the 5-9% range, irrespective of whether studies included only invasive cancers or DCIS as well, this figure masked a widely divergent bimodal range of estimates,46,69-113 including estimates from an Australian study that were at the high end of the range.88

A recent landmark UK review confirmed a lack of reliable data and considerable uncertainty around the extent of overdiagnosis and indicated that any estimate will be, at best, provisional.15 The provisional estimate of overdiagnosis from the UK Panel is in the range of 11-19%, expressed as a proportion of diagnosed cancers in women invited for screening. Another European review, including data from 7 countries, estimated overdiagnosis in the range of 1-10%, after adjusting for breast cancer risk and lead time.97 Based on the UK and European reviews,15,97 it is estimated that for every 1000 women in Australia who are screened every two years from age 50 to age 74, around 8 breast cancers are found and treated that would not have been found in a woman’s lifetime. This estimate of around 8 (between 2 and 21) breast cancers has been confirmed by results from cohort studies, including two cohort studies subsequently published in 2013.76,98,114

Conclusion

Mammographic screening has been shown from randomised trials and from observational studies to reduce mortality from breast cancer.1-12 Evaluations of mammographic screening from observational studies in Australia and Europe have provided broadly consistent results and have indicated breast cancer reductions in screening participants higher than that estimated from trial data. The national BreastScreen Australia Evaluation indicated a reduction in breast cancer mortality at a population level for the target age group of 50-69 years of approximately 21-28% at the participation level of 56%.19

“Overdiagnosis” from breast screening does not refer to error or misdiagnosis, but rather refers to breast cancer diagnosed by screening that might never have progressed to become symptomatic in a woman’s lifetime. It is likely that despite uncertainties about the extent of overdiagnosis, there would be a subset of screen-detected invasive and pre-invasive cancers that would progress very slowly if at all. If distinguishing features could be identified for such cancers, it may be possible to determine subsets of cancers that may be treated more conservatively, if at all. Molecular and genomic research is needed to find means of identifying, with enough certainty, which cancers are at minimal risk of progression and therefore could be managed more conservatively.115-127

Access to information about the benefits of mammographic screening as well as the risks, including overdiagnosis, can assist women to make informed decisions about screening participation.

Information about mammographic screening for women is available online: BreastScreen and You.

*On 30 June 2011, National Breast and Ovarian Cancer Centre (NBOCC) amalgamated with Cancer Australia to form a single national agency, Cancer Australia, to provide leadership in cancer control and improve outcomes for Australians affected by cancer.

[accordion collapsed]

References

  1. International Agency for Research on Cancer IARC. IARC Handbooks of Cancer Prevention. Vol. 7: Breast Cancer Screening. World Health Organization, Lyon, 2002.
  2. Andersson I, Aspegren K, Janzon L, et al. Mammographic screening and mortality from breast cancer: the Malmo mammographic screening trial. BMJ. 1988;297(6654):943-8.
  3. Demissie K, Mills OF and Rhoads GG. Empirical comparison of the results of randomized controlled trials and case-control studies in evaluating the effectiveness of screening mammography. J Clin Epidemiol. 1998;51(2):81-91.
  4. Frisell J, Eklund G, Hellstrom L, et al. Randomized study of mammography screening--preliminary report on mortality in the Stockholm trial. Breast Cancer Res Treat. 1991;18(1):49-56.
  5. Miller AB, Baines CJ, To T and Wall C. Canadian National Breast Screening Study: 2. Breast cancer detection and death rates among women aged 50 to 59 years. CMAJ. 1992;147(10):1477-88.
  6. Miller AB, Baines CJ, To T and Wall C. Canadian National Breast Screening Study: 1. Breast cancer detection and death rates among women aged 40 to 49 years. CMAJ. 1992;147(10):1459-76.
  7. Nystrom L, Andersson I, Bjurstam N, et al. Long-term effects of mammography screening: updated overview of the Swedish randomised trials. Lancet. 2002;359(9310):909-19.
  8. Nystrom L, Rutqvist LE, Wall S, et al. Breast cancer screening with mammography: overview of Swedish randomised trials. Lancet. 1993;341(8851):973-8.
  9. Rijnsburger AJ, van Oortmarssen GJ, Boer R, et al. Mammography benefit in the Canadian National Breast Screening Study-2: a model evaluation. Int J Cancer. 2004;110(5):756-62.
  10. Roberts MM, Alexander FE, Anderson TJ, et al. Edinburgh trial of screening for breast cancer: mortality at seven years. Lancet. 1990;335(8684):241-6.
  11. Shapiro S, Venet W, Strax P, et al. Selection, follow-up, and analysis in the Health Insurance Plan Study: a randomized trial with breast cancer screening. Natl Cancer Inst Monogr. 1985;67(65-74.
  12. Tabar L, Fagerberg G, Duffy SW, et al. Update of the Swedish two-county program of mammographic screening for breast cancer. Radiol Clin North Am. 1992;30(1):187-210.
  13. Glasziou P and Houssami N. The evidence base for breast cancer screening. Prev Med. 2011;53(3):100-2.
  14. Gotzsche PC and Nielsen M. Screening for breast cancer with mammography. Cochrane Database Syst Rev. 2009;4):CD001877.
  15. Marmot MGAD, Cameron D, Dewar J, Thompson S, Wilcox M. The benefits and harms of breast cancer screening: an independent review. Cancer Research UK and Department of Health (England), England, 2012.
  16. Taylor R, Morrell S, Estoesta J and Brassil A. Mammography screening and breast cancer mortality in New South Wales, Australia. Cancer Causes Control. 2004;15(6):543-50.
  17. Roder D, Houssami N, Farshid G, et al. Population screening and intensity of screening are associated with reduced breast cancer mortality: evidence of efficacy of mammography screening in Australia. Breast Cancer Res Treat. 2008;108(3):409-16.
  18. Nickson C, Mason KE, English DR and Kavanagh AM. Mammographic screening and breast cancer mortality: a case-control study and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2012;21(9):1479-88.
  19. Australian Department of Health and Ageing. BreastScreen Australia Evaluation. Screening Monograph No.4/2009. Mortality (ecological) study. Australian Government Department of Health and Ageing, Canberra, 2009.
  20. Morrell S, Taylor R, Roder D and Dobson A. Mammography screening and breast cancer mortality in Australia: an aggregate cohort study. J Med Screen. 2012;19(1):26-34.
  21. Autier P, Boniol M, Gavin A and Vatten LJ. Breast cancer mortality in neighbouring European countries with different levels of screening but similar access to treatment: trend analysis of WHO mortality database. BMJ. 2011;343(d4411.
  22. Broeders M, Moss S, Nystrom L, et al. The impact of mammographic screening on breast cancer mortality in Europe: a review of observational studies. J Med Screen. 2012;19 Suppl 1(14-25.
  23. Broeders MJ, Verbeek AL, Straatman H, et al. Repeated mammographic screening reduces breast cancer mortality along the continuum of age. J Med Screen. 2002;9(4):163-7.
  24. Elmore JG, Reisch LM, Barton MB, et al. Efficacy of breast cancer screening in the community according to risk level. J Natl Cancer Inst. 2005;97(14):1035-43.
  25. Esserman L and Thompson I. Solving the overdiagnosis dilemma. J Natl Cancer Inst. 2010;102(9):582-3.
  26. Fielder HM, Warwick J, Brook D, et al. A case-control study to estimate the impact on breast cancer death of the breast screening programme in Wales. J Med Screen. 2004;11(4):194-8.
  27. Gabe R and Duffy SW. Evaluation of service screening mammography in practice: the impact on breast cancer mortality. Ann Oncol. 2005;16 Suppl 2(ii153-62.
  28. Gabe R, Tryggvadottir L, Sigfusson BF, et al. A case-control study to estimate the impact of the Icelandic population-based mammography screening program on breast cancer death. Acta Radiol. 2007;48(9):948-55.
  29. Jorgensen KJ, Zahl PH and Gotzsche PC. Breast cancer mortality in organised mammography screening in Denmark: comparative study. BMJ. 2010;340(c1241.
  30. Kalager M, Zelen M, Langmark F and Adami HO. Effect of screening mammography on breast-cancer mortality in Norway. N Engl J Med. 2010;363(13):1203-10.
  31. Miltenburg GA, Peeters PH, Fracheboud J and Collette HJ. Seventeen-year evaluation of breast cancer screening: the DOM project, The Netherlands. Diagnostisch Onderzoek (investigation) Mammacarcinoom. Br J Cancer. 1998;78(7):962-5.
  32. Moss SM, Nystrom L, Jonsson H, et al. The impact of mammographic screening on breast cancer mortality in Europe: a review of trend studies. J Med Screen. 2012;19 Suppl 1(26-32.
  33. Njor S, Nystrom L, Moss S, et al. Breast cancer mortality in mammographic screening in Europe: a review of incidence-based mortality studies. J Med Screen. 2012;19 Suppl 1(33-41.
  34. Norman SA, Russell Localio A, Weber AL, et al. Protection of mammography screening against death from breast cancer in women aged 40-64 years. Cancer Causes Control. 2007;18(9):909-18.
  35. Olsen AH, Njor SH, Vejborg I, et al. Breast cancer mortality in Copenhagen after introduction of mammography screening: cohort study. BMJ. 2005;330(7485):220.
  36. Otto SJ, Fracheboud J, Looman CW, et al. Initiation of population-based mammography screening in Dutch municipalities and effect on breast-cancer mortality: a systematic review. Lancet. 2003;361(9367):1411-7.
  37. Paap E, Holland R, den Heeten GJ, et al. A remarkable reduction of breast cancer deaths in screened versus unscreened women: a case-referent study. Cancer Causes Control. 2010;21(10):1569-73.
  38. Paci E. Summary of the evidence of breast cancer service screening outcomes in Europe and first estimate of the benefit and harm balance sheet. J Med Screen. 2012;19 Suppl 1(5-13.
  39. Schopper D and de Wolf C. How effective are breast cancer screening programmes by mammography? Review of the current evidence. Eur J Cancer. 2009;45(11):1916-23.
  40. Tabar L, Vitak B, Chen TH, et al. Swedish two-county trial: impact of mammographic screening on breast cancer mortality during 3 decades. Radiology. 2011;260(3):658-63.
  41. Van Dijck JA, Verbeek AL, Beex LV, et al. Breast-cancer mortality in a non-randomized trial on mammographic screening in women over age 65. Int J Cancer. 1997;70(2):164-8.
  42. Zahl PH, Maehlen J and Welch HG. The natural history of invasive breast cancers detected by screening mammography. Arch Intern Med. 2008;168(21):2311-6.
  43. Otto SJ, Fracheboud J, Verbeek AL, et al. Mammography screening and risk of breast cancer death: a population-based case-control study. Cancer Epidemiol Biomarkers Prev. 2012;21(1):66-73.
  44. Burton RC, Bell RJ, Thiagarajah G and Stevenson C. Adjuvant therapy, not mammographic screening, accounts for most of the observed breast cancer specific mortality reductions in Australian women since the national screening program began in 1991. Breast Cancer Res Treat. 2012;131(3):949-55.
  45. Berry DA, Cronin KA, Plevritis SK, et al. Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med. 2005;353(17):1784-92.
  46. Duffy SW, McCann J, Godward S, et al. Some issues in screening for breast and other cancers. J Med Screen. 2006;13 Suppl 1(S28-34.
  47. Welch HG. Overdiagnosis and mammography screening. BMJ. 2009;339(b1425.
  48. Welch HG and Black WC. Overdiagnosis in cancer. J Natl Cancer Inst. 2010;102(9):605-13.
  49. Dussan C, Zubor P, Fernandez M, et al. Spontaneous regression of a breast carcinoma: a case report. Gynecol Obstet Invest. 2008;65(3):206-11.
  50. Krutchik AN, Buzdar AU, Blumenschein GR and Lukeman JM. Spontaneous regression of breast carcinoma. Arch Intern Med. 1978;138(11):1734-5.
  51. Alexander FE, Anderson TJ, Brown HK, et al. 14 years of follow-up from the Edinburgh randomised trial of breast-cancer screening. Lancet. 1999;353(9168):1903-8.
  52. Bjurstam N, Bjorneld L, Warwick J, et al. The Gothenburg Breast Screening Trial. Cancer. 2003;97(10):2387-96.
  53. Frisell J, Lidbrink E, Hellstrom L and Rutqvist LE. Followup after 11 years--update of mortality results in the Stockholm mammographic screening trial. Breast Cancer Res Treat. 1997;45(3):263-70.
  54. Miller AB, To T, Baines CJ and Wall C. Canadian National Breast Screening Study-2: 13-year results of a randomized trial in women aged 50-59 years. J Natl Cancer Inst. 2000;92(18):1490-9.
  55. Miller AB, To T, Baines CJ and Wall C. The Canadian National Breast Screening Study-1: breast cancer mortality after 11 to 16 years of follow-up. A randomized screening trial of mammography in women age 40 to 49 years. Ann Intern Med. 2002;137(5 Part 1):305-12.
  56. Shapiro S. Periodic screening for breast cancer: the HIP Randomized Controlled Trial. Health Insurance Plan. J Natl Cancer Inst Monogr. 1997;22):27-30.
  57. Tabar L, Vitak B, Chen HH, et al. The Swedish Two-County Trial twenty years later. Updated mortality results and new insights from long-term follow-up. Radiol Clin North Am. 2000;38(4):625-51.
  58. Zackrisson S, Andersson I, Janzon L, et al. Rate of over-diagnosis of breast cancer 15 years after end of Malmo mammographic screening trial: follow-up study. BMJ. 2006;332(7543):689-92.
  59. Biesheuvel C, Barratt A, Howard K, et al. Effects of study methods and biases on estimates of invasive breast cancer overdetection with mammography screening: a systematic review. Lancet Oncol. 2007;8(12):1129-38.
  60. Duffy SW, Agbaje O, Tabar L, et al. Overdiagnosis and overtreatment of breast cancer: estimates of overdiagnosis from two trials of mammographic screening for breast cancer. Breast Cancer Res. 2005;7(6):258-65.
  61. Duffy SW, Tabar L, Olsen AH, et al. Absolute numbers of lives saved and overdiagnosis in breast cancer screening, from a randomized trial and from the Breast Screening Programme in England. J Med Screen. 2010;17(1):25-30.
  62. Gotzsche PC. Ramifications of screening for breast cancer: overdiagnosis in the Malmo trial was considerably underestimated. BMJ. 2006;332(7543):727.
  63. Gotzsche PC, Hartling OJ, Nielsen M, et al. Breast screening: the facts--or maybe not. BMJ. 2009;338(b86.
  64. Moss S. Overdiagnosis and overtreatment of breast cancer: overdiagnosis in randomised controlled trials of breast cancer screening. Breast Cancer Res. 2005;7(5):230-4.
  65. Nelson HD, Tyne K, Naik A, et al. Screening for breast cancer: an update for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;151(10):727-37, W237-42.
  66. Veronesi A and Serraino D. Screening: is breast cancer overdiagnosed? Nat Rev Clin Oncol. 2009;6(12):682-3.
  67. Welch HG, Schwartz LM and Woloshin S. Ramifications of screening for breast cancer: 1 in 4 cancers detected by mammography are pseudocancers. BMJ. 2006;332(7543):727.
  68. Woloshin S and Schwartz LM. The benefits and harms of mammography screening: understanding the trade-offs. JAMA. 2010;303(2):164-5.
  69. Advisory Committee on Breast Cancer Screening. Screening for breast cancer in England: past and future. J Med Screen. 2006;13(2):59-61.
  70. Allgood PC, Duffy SW, Kearins O, et al. Explaining the difference in prognosis between screen-detected and symptomatic breast cancers. Br J Cancer. 2011;104(11):1680-5.
  71. Anttila A, Koskela J and Hakama M. Programme sensitivity and effectiveness of mammography service screening in Helsinki, Finland. J Med Screen. 2002;9(4):153-8.
  72. Bleyer A and Welch HG. Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med. 2012;367(21):1998-2005.
  73. Ciatto S. The overdiagnosis nightmare: a time for caution. BMC Womens Health. 2009;9(34.
  74. de Gelder R, Heijnsdijk EA, van Ravesteyn NT, et al. Interpreting overdiagnosis estimates in population-based mammography screening. Epidemiol Rev. 2011;33(1):111-21.
  75. de Koning HJ, Draisma G, Fracheboud J and de Bruijn A. Overdiagnosis and overtreatment of breast cancer: microsimulation modelling estimates based on observed screen and clinical data. Breast Cancer Res. 2006;8(1):202.
  76. Falk RS, Hofvind S, Skaane P and Haldorsen T. Overdiagnosis among women attending a population-based mammography screening program. Int J Cancer. 2013;133(3):705-712.
  77. Gotzsche PC. On the benefits and harms of screening for breast cancer. Int J Epidemiol. 2004;33(1):56-64.
  78. Gotzsche PC, Jorgensen KJ, Zahl PH and Maehlen J. Why mammography screening has not lived up to expectations from the randomised trials. Cancer Causes Control. 2012;23(1):15-21.
  79. Hellquist BN, Duffy SW, Nystrom L and Jonsson H. Overdiagnosis in the population-based service screening programme with mammography for women aged 40 to 49 years in Sweden. J Med Screen. 2012;19(1):14-9.
  80. Jonsson H, Johansson R and Lenner P. Increased incidence of invasive breast cancer after the introduction of service screening with mammography in Sweden. Int J Cancer. 2005;117(5):842-7.
  81. Jorgensen KJ and Gotzsche PC. Overdiagnosis in publicly organised mammography screening programmes: systematic review of incidence trends. BMJ. 2009;339(b2587.
  82. Jorgensen KJ, Zahl PH and Gotzsche PC. Overdiagnosis in organised mammography screening in Denmark. A comparative study. BMC Womens Health. 2009;9(36.
  83. Kalager M, Adami HO, Bretthauer M and Tamimi RM. Overdiagnosis of invasive breast cancer due to mammography screening: results from the Norwegian screening program. Ann Intern Med. 2012;156(7):491-9.
  84. Kopans DB, Smith RA and Duffy SW. Mammographic screening and "overdiagnosis". Radiology. 2011;260(3):616-20.
  85. Kumar AS, Bhatia V and Henderson IC. Overdiagnosis and overtreatment of breast cancer: rates of ductal carcinoma in situ: a US perspective. Breast Cancer Res. 2005;7(6):271-5.
  86. McCann J, Treasure P and Duffy S. Modelling the impact of detecting and treating ductal carcinoma in situ in a breast screening programme. J Med Screen. 2004;11(3):117-25.
  87. Moller H and Davies E. Over-diagnosis in breast cancer screening. BMJ. 2006;332(7543):691-2.
  88. Morrell S, Barratt A, Irwig L, et al. Estimates of overdiagnosis of invasive breast cancer associated with screening mammography. Cancer Causes Control. 2010;21(2):275-82.
  89. Olsen AH, Agbaje OF, Myles JP, et al. Overdiagnosis, sojourn time, and sensitivity in the Copenhagen mammography screening program. Breast J. 2006;12(4):338-42.
  90. Olsen AH, Jensen A, Njor SH, et al. Breast cancer incidence after the start of mammography screening in Denmark. Br J Cancer. 2003;88(3):362-5.
  91. Olsen O and Gotzsche PC. Cochrane review on screening for breast cancer with mammography. Lancet. 2001;358(9290):1340-2.
  92. Paci E, Duffy, S.W., Giorgi, D., Prevost, T.C., Rosselli del Turco, M. Population-based breast cancer screening programmes: estimates of sensitivity, overdiagnosis and early prediction of the benefit. Quantitive methods for the evaluation of cancer screening, ed. S.W. Duffy, Hill, C., Esteve, J. 2001, Arnold: London. 127-35. Arnold, London, 2001.
  93. Paci E and Duffy S. Overdiagnosis and overtreatment of breast cancer: overdiagnosis and overtreatment in service screening. Breast Cancer Res. 2005;7(6):266-70.
  94. Paci E, Miccinesi G, Puliti D, et al. Estimate of overdiagnosis of breast cancer due to mammography after adjustment for lead time. A service screening study in Italy. Breast Cancer Res. 2006;8(6):R68.
  95. Paci E, Warwick J, Falini P and Duffy SW. Overdiagnosis in screening: is the increase in breast cancer incidence rates a cause for concern? J Med Screen. 2004;11(1):23-7.
  96. Peeters PH, Verbeek AL, Straatman H, et al. Evaluation of overdiagnosis of breast cancer in screening with mammography: results of the Nijmegen programme. Int J Epidemiol. 1989;18(2):295-9.
  97. Puliti D, Duffy SW, Miccinesi G, et al. Overdiagnosis in mammographic screening for breast cancer in Europe: a literature review. J Med Screen. 2012;19 Suppl 1(42-56.
  98. Puliti D, Miccinesi G, Zappa M, et al. Balancing harms and benefits of service mammography screening programs: a cohort study. Breast Cancer Res. 2012;14(1):R9.
  99. Puliti D, Zappa M, Miccinesi G, et al. An estimate of overdiagnosis 15 years after the start of mammographic screening in Florence. Eur J Cancer. 2009;45(18):3166-71.
  100. Ravdin PM, Cronin KA, Howlader N, et al. The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med. 2007;356(16):1670-4.
  101. Seigneurin A, Francois, O., Labarere, J., Oudeville, P., Monlong, J., Colonna, M. . Overdiagnosis from non-progressive cancer detected by screening mammography: Stochastic simulation study with calibration to population based registry data. BMJ. 2011;343(d7017.
  102. Svendsen AL, Olsen AH, von Euler-Chelpin M and Lynge E. Breast cancer incidence after the introduction of mammography screening: what should be expected? Cancer. 2006;106(9):1883-90.
  103. de Koning HJ, van Ineveld BM, van Oortmarssen GJ, et al. Breast cancer screening and cost-effectiveness; policy alternatives, quality of life considerations and the possible impact of uncertain factors. Int J Cancer. 1991;49(4):531-537.
  104. Von Euler-Chelpin M. NSH, Lynge E. . Response to Jorgensen K.J., Gotzsche P. Overdiagnosis in publicly organised mammography screening programmes: Systematic review of incidence trends. BMJ. 2009;339.
  105. Waller M, Moss S, Watson J and Moller H. The effect of mammographic screening and hormone replacement therapy use on breast cancer incidence in England and Wales. Cancer Epidemiol Biomarkers Prev. 2007;16(11):2257-61.
  106. Yen AM, Duffy SW, Chen TH, et al. Long-term incidence of breast cancer by trial arm in one county of the Swedish Two-County Trial of mammographic screening. Cancer. 2012;118(23):5728-32.
  107. Yen MF, Tabar L, Vitak B, et al. Quantifying the potential problem of overdiagnosis of ductal carcinoma in situ in breast cancer screening. Eur J Cancer. 2003;39(12):1746-54.
  108. Zahl PH. Overdiagnosis of invasive breast cancer due to mammography screening. Ann Intern Med. 2012;157(3):220-1; author reply 221-2.
  109. Zahl PH and Maehlen J. Overdiagnosis in mammography screening. Tidsskr Nor Laegeforen. 2004;124(17):2238-9.
  110. Zahl PH and Maehlen J. Overdiagnosis of breast cancer after 14 years of mammography screening. Tidsskr Nor Laegeforen. 2012;132(4):414-7.
  111. Zahl PH, Strand BH and Maehlen J. Incidence of breast cancer in Norway and Sweden during introduction of nationwide screening: prospective cohort study. BMJ. 2004;328(7445):921-4.
  112. Dobson HM and Thomas JS. Breast screening overdiagnosis. Protocols are evidence based. BMJ. 2009;11(339):b3262.
  113. Gunsoy NB, Garcia-Closas M and Moss SM. Modelling the overdiagnosis of breast cancer due to mammography screening in women aged 40-49 in the United Kingdom. Breast Cancer Res. 2012;14(6):R152.
  114. Njor SH, Olsen AH, Blichert-Toft M, et al. Overdiagnosis in screening mammography in Denmark: population based cohort study. BMJ. 2013;346(f1064.
  115. Abd El-Rehim DM, Ball G, Pinder SE, et al. High-throughput protein expression analysis using tissue microarray technology of a large well-characterised series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses. Int J Cancer. 2005;116(3):340-50.
  116. Boland GP, Knox WF and Bundred NJ. Molecular markers and therapeutic targets in ductal carcinoma in situ. Microsc Res Tech. 2002;59(1):3-11.
  117. Coates AS, Millar EK, O'Toole SA, et al. Prognostic interaction between expression of p53 and estrogen receptor in patients with node-negative breast cancer: results from IBCSG Trials VIII and IX. Breast Cancer Res. 2012;14(6):R143.
  118. de Roos MA, van der Vegt B, de Vries J, et al. Pathological and biological differences between screen-detected and interval ductal carcinoma in situ of the breast. Ann Surg Oncol. 2007;14(7):2097-104.
  119. Evans AJ, Pinder SE, Ellis IO and Wilson AR. Screen detected ductal carcinoma in situ (DCIS): overdiagnosis or an obligate precursor of invasive disease? J Med Screen. 2001;8(3):149-51.
  120. Goldhirsch A, Ingle JN, Gelber RD, et al. Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol. 2009;20(8):1319-29.
  121. Ho GH, Calvano JE, Bisogna M, et al. In microdissected ductal carcinoma in situ, HER-2/neu amplification, but not p53 mutation, is associated with high nuclear grade and comedo histology. Cancer. 2000;89(11):2153-60.
  122. Iacoangeli A, Lin Y, Morley EJ, et al. BC200 RNA in invasive and preinvasive breast cancer. Carcinogenesis. 2004;25(11):2125-33.
  123. Leal CB, Schmitt FC, Bento MJ, et al. Ductal carcinoma in situ of the breast. Histologic categorization and its relationship to ploidy and immunohistochemical expression of hormone receptors, p53, and c-erbB-2 protein. Cancer. 1995;75(8):2123-31.
  124. Mack L, Kerkvliet N, Doig G and O'Malley FP. Relationship of a new histological categorization of ductal carcinoma in situ of the breast with size and the immunohistochemical expression of p53, c-erb B2, bcl-2, and ki-67. Hum Pathol. 1997;28(8):974-9.
  125. Ottesen GL. Carcinoma in situ of the female breast. A clinico-pathological, immunohistological, and DNA ploidy study. APMIS Suppl. 2003;108):1-67.
  126. Rakha EA, Armour JA, Pinder SE, et al. High-resolution analysis of 16q22.1 in breast carcinoma using DNA amplifiable probes (multiplex amplifiable probe hybridization technique) and immunohistochemistry. Int J Cancer. 2005;114(5):720-9.
  127. van't Veer LJ and Bernards R. Enabling personalized cancer medicine through analysis of gene-expression patterns. Nature. 2008;452(7187):564-70.

[/accordion]