Karsten Juhl Jørgensen, MD, DrMedSci; Peter C. Gøtzsche, MD, MSc; Mette Kalager, MD, PhD (*); Per-Henrik Zahl, MD, DrMedSci (*)
Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-0270.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol and statistical code: Available from Dr. Jørgensen (e-mail, firstname.lastname@example.org). Data set: The aggregated statistical data available from Dr. Jørgensen (e-mail, email@example.com); however, under Danish legislation, the authors are not at liberty to share individual-patient data from registries.
Requests for Single Reprints: Karsten Juhl Jørgensen, MD, DrMedSci, The Nordic Cochrane Centre, Rigshospitalet, Department 7811, Blegdamsvej 9, DK-2100 Copenhagen, Denmark; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Jørgensen and Gøtzsche: The Nordic Cochrane Centre, Rigshospitalet, Department 7811, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Dr. Kalager: University of Oslo, Institute of Health and Society, Department of Health Management and Health Economics, PO Box 1089, Blindern, 0318 Oslo, Norway.
Dr. Zahl: Norwegian Institute of Public Health, PO Box 4404, Nydalen, N-0403 Oslo, Norway.
Author Contributions: Conception and design: K.J. Jørgensen, P.C. Gøtzsche, M. Kalager, P.H. Zahl.
Analysis and interpretation of the data: K.J. Jørgensen, P.C. Gøtzsche, M. Kalager, P.H. Zahl.
Drafting of the article: K.J. Jørgensen, M. Kalager, P.H. Zahl.
Critical revision of the article for important intellectual content: K.J. Jørgensen, P.C. Gøtzsche, M. Kalager, P.H. Zahl.
Final approval of the article: K.J. Jørgensen, P.C. Gøtzsche, M. Kalager, P.H. Zahl.
Statistical expertise: K.J. Jørgensen, M. Kalager, P.H. Zahl.
Administrative, technical, or logistic support: P.C. Gøtzsche.
Collection and assembly of data: P.H. Zahl.
Effective breast cancer screening should detect early-stage cancer and prevent advanced disease.
To assess the association between screening and the size of detected tumors and to estimate overdiagnosis (detection of tumors that would not become clinically relevant).
Denmark from 1980 to 2010.
Women aged 35 to 84 years.
Screening programs offering biennial mammography for women aged 50 to 69 years beginning in different regions at different times.
Trends in the incidence of advanced (>20 mm) and nonadvanced (≤20 mm) breast cancer tumors in screened and nonscreened women were measured. Two approaches were used to estimate the amount of overdiagnosis: comparing the incidence of advanced and nonadvanced tumors among women aged 50 to 84 years in screening and nonscreening areas; and comparing the incidence for nonadvanced tumors among women aged 35 to 49, 50 to 69, and 70 to 84 years in screening and nonscreening areas.
Screening was not associated with lower incidence of advanced tumors. The incidence of nonadvanced tumors increased in the screening versus prescreening periods (incidence rate ratio, 1.49 [95% CI, 1.43 to 1.54]). The first estimation approach found that 271 invasive breast cancer tumors and 179 ductal carcinoma in situ (DCIS) lesions were overdiagnosed in 2010 (overdiagnosis rate of 24.4% [including DCIS] and 14.7% [excluding DCIS]). The second approach, which accounted for regional differences in women younger than the screening age, found that 711 invasive tumors and 180 cases of DCIS were overdiagnosed in 2010 (overdiagnosis rate of 48.3% [including DCIS] and 38.6% [excluding DCIS]).
Regional differences complicate interpretation.
Breast cancer screening was not associated with a reduction in the incidence of advanced cancer. It is likely that 1 in every 3 invasive tumors and cases of DCIS diagnosed in women offered screening represent overdiagnosis (incidence increase of 48.3%).
Three-year moving averages of advanced breast tumors (>20 mm) in women aged 35 to 49 y (A), 50 to 69 y (B), and 70 to 84 y (C).
The vertical dotted lines indicate the year of introduction of breast screening in Copenhagen (1991), Funen (1994), and the remaining regions in Denmark (2007). (See Supplement Figure 4, for separate incidence rates for Copenhagen and Funen.)
Table 1. Annual Percentage of Change in Incidence (95% CI) in the Screening and Nonscreening Areas Before and After Screening for Advanced and Nonadvanced Cancer in Different Age Groups*
Table 2. IRs per 100 000 Person-Years of Breast Cancer and IRRs in the Screening and Nonscreening Areas Before and After Screening for Advanced and Nonadvanced Cancer in Different Age Groups*
Three-year moving averages of nonadvanced breast tumors (≤20 mm) in women aged 35 to 49 y (A), 50 to 69 y (B), and 70 to 84 y (C).
The vertical dotted lines indicate the year of introduction of breast screening in Copenhagen (1991), Funen (1994), and the remaining regions in Denmark (2007). (See Supplement Figure 5, for separate incidence rates for Copenhagen and Funen.) DCIS = ductal carcinoma in situ.
Table 3. IRs per 100 000 Person-Years Among Women Aged 50 to 84 y (Approach 1) and 50 to 69 y (Approach 2) in Different Areas Before and After Screening, by Type of Cancer*
Table 4. Overdiagnosis in 2010 According to the Average Incidence Method*
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John D. Keen, MD
John H. Stroger Hospital of Cook County, Chicago
January 10, 2017
Read the study before criticizing it.
The Society of Breast Imaging has already criticized this work on January 9: http://www.sbi-online.org/NEWS/IntheNews/TabId/104/ArtMID/1327/ArticleID/497/ACR-SBI-J248rgensen-Et-Al-Mammography-Data-Does-Not-Support-Study-Conclusions.aspxThis Annals study on overdiagnosis was published January 10 and has a contemporary control group which is not available in the United States, making a valuable contribution to the overdiagnosis debate. Given the press embargo it is uncertain how the SBI experts could have thoroughly read the study. Perhaps they will comment in more detail so the authors can respond to any legitimate concerns.
Alain Braillon M.D., Ph.D
University Hospital, Cedex
January 11, 2017
Breast cancer screening: The bazaar of public health.
The Danish cohort study breast cancer screening was not associated with a reduction in the incidence of advanced cancer and 1 in every 3 invasive tumors and cases of ductal carcinoma in situ diagnosed were overdiagnosis.(1)Year after year expected benefits of screening have been vanishing while evidence of harms has been growing.(2,3)Sadly, the flow of misleading advertising claims on the Internet from advocates, some well-intentioned, of the “pink ribbon” cause-related marketing remains out of control. Even the best professional organisations can hardly avoid semantical pitfalls. Eg. “All women should be familiar with the known benefits, limitations, and potential harms linked to breast cancer screening” (http://www.cancer.org/healthy/findcancerearly/cancerscreeningguidelines/american-cancer-society-guidelines-for-the-early-detection-of-cancer) as if benefits were known for sure and harms only potential!National agencies for health as well as professional organisations have chosen the ostrich policy vs a U-turn or a moratorium, for the extremes. Indeed, there are no concerns for even the minimum minimorum (the least of all minimums) yet: Who provide evidenced based decision aids for informed consent (pictographs with absolute numbers using a consistent denominator, time frames and visuals employing the same scale for information on gains and losses of the options)?(4) Only the Belgian Health Care Knowledge Centre (https://kce.fgov.be/sites/default/files/page_documents/KCE_216_breast_cancer_screening.pdf), although few independent initiatives can exist.(https://www.cancer-rose.fr/wp-content/plugins/download-attachments/includes/download.php?id=32)The basic Food, Drug, and Cosmetic Act of 1938 and its amendments have given the Food and Drug Administration the authority for providing the public with an unsurpassed degree of efficacy and safety of drugs and for regulating advertising.(5) Public health, in 2017, remains offside. 1 Jørgensen KJ; Gøtzsche PG, Kalager M, Zahl PH. Breast cancer screening in Denmark: A cohort study of tumor size and overdiagnosis. Ann Intern Med 2017. Online. DOI: 10.7326/M16-02702 Gøtzsche PC, Nielsen M. Screening for breast cancer with mammography. Cochrane Database Syst Rev 2009;(4):CD001877.3 Nelson HD, Pappas M, Cantor A, Griffin J, Daeges M, Humphrey L. Harms of Breast Cancer Screening: Systematic review to update the 2009 U.S. Preventive Services Task Force Recommendation. Ann Intern Med 2016;164:256-67.4 Hersch J, Barratt A, Jansen J, et al. Use of a decision aid including information on overdetection to support informed choice about breast cancer screening: a randomised controlled trial. Lancet 2015;385:1642–52.5 Sadusk JF Jr. Drugs and the public safety. Ann Intern Med 1966;65:849-56.
Elsebeth Lynge, Anna-Belle Beau, Peer Christiansen, Niels Kroman, Sisse Njor, Ilse Vejborg
Department of Public Health, University of Copenhagen
January 25, 2017
Calculations and design are problematic.
Jørgensen et al.(1) estimated overdiagnosis in breast cancer screening in Denmark. Their approaches are problematic as well as their data. First approach builds on absolute differences in age 50-84 weighted by after period incidence in non-screening area, resulting in an overdiagnosis of 9.9%. But relative changes without weights show overdiagnosis of 1% (= (351.3 x 182.4)/(226.1 x 280)). Anyhow, both calculations are problematic, due to limitations in study design, see below.Second approach builds on absolute differences in nonadvanced tumors in age 50-69 weighted by after period incidence in non-screening area, resulting in an overdiagnosis of 48%, meaning that ”1 in every 3 women aged 50 to 69 years diagnosed with breast cancer was overdiagnosed”. In the studied screening areas, screen-detected tumors constituted 54% of all tumors (screen-detected, interval cancers, and tumors in nonparticipants) when DCIS was included, and 51% when only invasive tumors were included (2). Overdiagnosis can affect only the screen-detected part of the tumors. With Jørgensen et al.’s calculation, more than half of invasive breast cancers detected at screening should thus be without potential to become a disease in the women’s life time – is this realistic? However, the key problem with the Jørgensen study is the design. Screening changes the age-specific pattern of breast cancer incidence in the targeted birth cohorts (3), including a prevalence peak during the first screen, an artificial aging during the subsequent screens, and a compensatory decrease after end of screening age (4). For women ”no longer offered screening”, Jørgensen et al. used data for women aged 70-84 year in 1991-2010 from Copenhagen and Frederiksberg and from 1994-2010 for Funen. But these data include observations from some women never offered screening; some still invited despite over age 70; and some women followed past the 8 years’ of the compensatory decrease (5). It is not possible to capture correctly the size of overdiagnosis with such crude data. Screening affects the age-specific incidence of breast cancer in cohorts of screened women, but this classic wisdom has not yet entered mainstream epidemiology. Studies of overdiagnosis are still published without proper considerabtion of the cohort perspective, and the study by Jørgensen et al. is an example. For the sake of screened women, researchers and journal editors should join efforts to find the best method for estimation of overdiagnosis. REFERENCES1. Jørgensen K, Gøtzsche P, Kalager M, Zahl P. Breast Cancer Screening in Denmark: A cohort study of tumor size and overdiagnosis. Ann Intern Med. [Epub ahead of print 10 January 2017] doi:10.7326/M16-0270. 2. Domingo L, Jacobsen KK, Euler-Chelpin M von, Vejborg I, Schwartz W, Sala M, et al. Seventeen-years overview of breast cancer inside and outside screening in Denmark. Acta Oncol. 2013 Jan 1;52(1):48–56. 3. Boer R, Warmerdam P, de Koning H, van Oortmarssen G. Extra incidence caused by mammographic screening. The Lancet. 1994 Apr 16;343(8903):979. 4. Møller B, Weedon-Fekjaer H, Hakulinen T, Tryggvadóttir L, Storm HH, Talbäck M, et al. The influence of mammographic screening on national trends in breast cancer incidence. Eur J Cancer Prev Off J Eur Cancer Prev Organ ECP. 2005 Apr;14(2):117–28. 5. Njor SH, Olsen AH, Blichert-Toft M, Schwartz W, Vejborg I, Lynge E. Overdiagnosis in screening mammography in Denmark: population based cohort study. BMJ. 2013 Feb 26;346:f1064.
Johannes P. van Netten Ph.D., Stephen Hoption Cann Ph.D., Ian Thornton M.Sc., Rory P Finegan M.Sc. FIBMS
Island Health Authority, University of British Columbia, University of Victoria
February 2, 2017
Why is mammography not useful in preventing of disease-specific mortality?
A positive mammogram can lead to the removal of potentially aggressive cancer tissue with the aim that it prevents further cancer development. A noble goal unless the procedure itself can cause an increased risk of progression. As early as 1994 (1) we published about this possibility but, in general, these warnings have not been taken seriously. Again, like many others, the latest results from the Danish breast cancer screening study (2) reported in this journal indicate that something is really wrong with the present screening procedure for breast cancer detection. It has not prevented disease-specific mortality. We have suggested that the procedure itself may be suspect due to injury from tissue compression and reported a case of an aggressive tumor that rapidly developed following a hematoma caused by the compression (3). Compressive injury can result in the release of growth factors that could accelerate tumor growth. This is particularly true for tumors that contain growth factors related to wound healing such as those that are Her2 positive. Thus, while screening may remove potential malignancies on the one hand, it may also augment the malignant potential of some tumors. Breast cancer screening methods that do not involve compression such as the more recent 3D imaging methods should replace this archaic method as quickly as possible.1 van Netten JP, Mogentale T, Ashwood-Smith MJ, Fletcher C, Coy P. Physical trauma and breast cancer. The Lancet 1994; 343: 978.2. Jorgensen KJ, Gotzsche PC, Galager M, Zahl P-H. Breast Cancer Screening In Denmark. A cohort study of tumor size and overdiagnosis. Ann Intern Med 2017.doi:10.7326/m16-02703. van Netten JP, Hoption-Cann S, Thornton I, Finegan R. Growing concern following compression mammography. BMJ Case Reports 2016. doi:10.1136/bcr-2016-216889
Changjun Wang, Yidong Zhou, Feng Mao, Yan Lin, Qiang Sun
Department of Breast Surgery, Peking Union Medical College Hospital
February 27, 2017
Screening Mammography did reduce the incidence of advanced tumor
Jørgensen and colleagues' study (1) concluded that mammography screening was not associated with lower incidence of advanced tumor, but increased the incidence of non-advanced cancer with incidence rate ratio (IRR) 1.49 (95% CI 1.43-1.54). The methodology used for IRR calculation could potentially undermine the strength of this study. The authors introduced IRR as the ratio of incidence rate “after screening” over “before screening”. In our opinion, similar to hazard ratio which was widely used for survival analysis, IRR would be more appropriate to be defined as ratio between experimental and control groups (screening and non-screening areas). Besides, the authors reached conclusion based on the assumption that no compensatory decrease of advanced cancer incidence in women aged 70-84 who no longer had screening could prove the existence of overdiagnosis. However, an opposite conclusion can be draw by reviewing data in Table 2. Except IRR of advanced cancer in 35-49 age group (screening area) decreased and 50-69 age group (screening area) maintained stable, all other groups in screening and non-screening areas showed increasing IRR and reached s significant increased breast cancer incidence. This supports the notion that a widespread increase of baseline breast cancer incidence exists all over the Denmark. Therefore, screening mammography did not exert its effect by directly reducing invasive cancer incidence, but by neutralizing the increase of baseline incidence and maintaining the incidence on a stable level. Conventionally, overdiagnosis was recognized as the diagnosis of cancers but not clinically evident of patient's lifetime, and it lacked a clearly-defined and operable concept. Any study of overdiagnosis should not only focus on “diagnosis”, but also the patient “prognosis”. Thus, instead of “incidence”, we suggested “mortality”, containing survival information, to be a better endpoint. A merit of this Denmark cohort is to have screening and non-screening areas at the same period, which made direct comparison possible and largely reduced the confounding effect caused by the advance of new treatments. We expected future studies could bring us more valuable information on cancer- specific or overall mortality and help to further assess the benefit of screening mammography. 1. Jørgensen KJ, Gøtzsche PC, Kalager M, Zahl P-H. Breast Cancer Screening in Denmark: A Cohort Study of Tumor Size and Overdiagnosis. Ann Intern Med. 2017 Jan 10; doi: 10.7326/M16-0270.
Sameer Bhargava MD, Kaitlyn Tsuruda MSc, Solveig Hofvind PhD
The Cancer Registry of Norway
Self-citations may not generate new evidence
We read with great interest the article by Jørgensen et al (1). The authors concluded no reduction in the incidence in advanced stage breast cancer occurred in Denmark after the introduction of organized screening. They further reported an overdiagnosis rate of 48.3%, and suggested that as many as a third of ductal carcinoma in situ and invasive breast cancers diagnosed in Danish women aged 50-69 were overdiagnosed. Based on their results, the authors claimed that screening has not led to a reduction in mortality, which contradicts a Danish study from 2015 (2). It is well known that Denmark has, for over 50 years, had the highest breast cancer incidence and mortality in Scandinavia (3). Only Copenhagen and Funen have offered women organized screening since 1991 and 1993, respectively; nationwide coverage was implemented in 2007.The authors note that their estimates of overdiagnosis are “similar to previous estimates” and proceed to cite three studies conducted by at least one member of the study group. Additionally, in their closing remarks, they summarize the implications of their findings and support their interpretation with four references. These four references were written by the study members alone, or included three of the four study members as co-authors. In fact, 10 of the 30 references cited in this paper include at least one of the study members as first or last author. Such references do not provide the reader sufficient information to evaluate the presented results in the context of the existing body of scientific knowledge.While we disagree with the authors’ methodological choices and conclusions, we do acknowledge the known challenges and lack of methodological consensus regarding the calculation of overdiagnosis. However, the estimates of overdiagnosis reported in this study are much higher than the majority of other studies (4, 5). Self-citation thus provides a means to spread fringe views on breast cancer screening that are unsupported by many other research groups.As members of the scientific community, we expect articles published in high-impact factor journals, such as the Annals of Internal Medicine, to point readers to work from the broader scientific literature and not that from individual research groups.In our view, this paper does not contribute to a better understanding of the effect of organized mammographic screening on tumor stage and overdiagnosis.1. Jorgensen KJ, Gotzsche PC, Kalager M, Zahl PH. Breast Cancer Screening in Denmark: A Cohort Study of Tumor Size and Overdiagnosis. Ann Intern Med. 2017 Jan 10. PubMed PMID: 28114661.2. Njor SH, Schwartz W, Blichert-Toft M, Lynge E. Decline in breast cancer mortality: how much is attributable to screening? J Med Screen. 2015 Mar;22(1):20-7. PubMed PMID: 25492943.3. Tryggvadottir L, Gislum M, Bray F, Klint A, Hakulinen T, Storm HH, et al. Trends in the survival of patients diagnosed with breast cancer in the Nordic countries 1964-2003 followed up to the end of 2006. Acta Oncol. 2010 Jun;49(5):624-31. PubMed PMID: 20429724.4. Marmot MG, Altman DG, Cameron DA, Dewar JA, Thompson SG, Wilcox M. The benefits and harms of breast cancer screening: an independent review. Br J Cancer. 2013 Jun 11;108(11):2205-40. PubMed PMID: 23744281. Pubmed Central PMCID: PMC3693450.5. Puliti D, Duffy SW, Miccinesi G, de Koning H, Lynge E, Zappa M, et al. Overdiagnosis in mammographic screening for breast cancer in Europe: a literature review. J Med Screen. 2012;19 Suppl 1:42-56. PubMed PMID: 22972810.
Tony H.H. Chen, Stephen W. Duffy
Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, UK
March 3, 2017
Breast Cancer Screening in Denmark
In their recent article, Jørgensen and colleagues compare changes over time, up to 2010, in large and small breast tumour incidence between areas of Denmark which had screening programmes and areas which had not. 1 They conclude that the screening had no effect on large tumour incidence and that there is substantial ovediagnosis. The data presented in the paper, however, indicate the opposite conclusions.(1) Table 2 in the paper shows very clearly that in the non-screening areas at ages 50-69, incidence of large tumours increased by 46%, whereas in the screening areas, the incidence of large tumours decreased by 4%. This indicates that the screening prevented large numbers of advanced cancers. The cross-product ratio from Table 2 ((112.2*82.2)/(117.0*120.1)) gives a reduction in advanced breast cancer associated with screening of 34% (RR=0.66, 95% CI:(0.61-0.71)). Comparisons across age groups are unreliable, since they are necessarily confounded by factors associated with age. For example, changes in neoadjuvant therapeutic practice over time are likely to be age-specific.(2) The above also indicates that many of the additional small tumours in the screening areas were not overdiagnosed but were cancers detected at a small size by screening which would otherwise have been diagnosed later as large tumours. Thus the authors’ second approach which assumes that the entire excess of small tumours in the screening areas and epochs are overdiagnosed, will greatly overestimate overdiagnosis. Their estimates from the first method, using all cancers, of 9.9-16.4%, will be closer to the truth. Even this will be an overestimate of overdiagnosis, since there will be some screen-detected cancers in the screening areas diagnosed close to 2010 which would have been diagnosed with symptoms after 2010. These are not overdiagnosed but diagnosed early.Thus the data presented by Jørgensen et al indicate, contrary to their conclusions, that the screening in Denmark has prevented large numbers of advanced breast cancers and has given rise to at worst modest levels of overdiagnosis.References1. Jørgensen KJ, Gøtzsche PC, Kalager M, Zahl PH. Breast cancer screening in Denmark: a cohort study of tumour size and overdiagnosis. Ann Intern Med 2017; 166: doi:10.7326/M16-0270
Karsten Juhl Jørgensen, Peter C. Gøtzsche, Mette Kalager, Per-Henrik Zahl
The Nordic Cochrane Center
May 9, 2017
Overdiagnosis of DCIS has become generally acknowledged, but some still find overdiagnosis of invasive breast cancers difficult to accept. However, our estimate of this is lower than estimates for PSA screening for prostate cancer, lung cancer screening with chest x-ray, neuroblastoma screening, and thyroid cancer screening.
The fundamental question is whether the observed increase in incidence with screening is caused by a desired advancement of the time of diagnosis or by overdiagnosis. If the observed substantial increase is not followed by a decline in incidence in previously screened age groups, the cause is overdiagnosis. While women aged 70 to 84 who have never attended screening may conceal a screening effect during the first years, this becomes irrelevant with 17 years of follow up. Gradually separating incidence curves for women 70 to 84 years are expected but there is no sign of this (Figures 1 C and 2 C ). Our sensitivity analysis following a closed cohort of individual women from age 60 to 75 years showed similar results (Supplement Figure 3 ).
Detection of DCIS should lead to fewer invasive cancers, but this was not observed. In contrast, removal of precursors with screening reduce incidence of invasive cervical and colorectal cancers.
Wang and colleagues seem to be more interested in an IRR comparing screening and non-screening areas. In a non-randomized setting, this introduces confounding since incidence differs between areas. Therefore, our before-after comparison of screening and non-screening areas is appropriate. They also request breast cancer-specific and total mortality. We previously assessed breast cancer mortality in Denmark and found no benefit . Total mortality was not reduced in the randomised trials (600,000 women) 
Bhargava and colleagues are correct that Denmark had the highest breast cancer incidence and mortality in Scandinavia for 50 years. However, although Denmark have had screening far shorter than Sweden, Finland, and parts of Norway, reductions in breast cancer mortality from 1989 to 2006 among women 50 to 69 years were greater in Denmark (26%) than in Sweden (16 %), Finland (11 %), and Norway (23 %). Across Europe, reductions were greatest in women below the screening age . Our choice of references was based on a recent independent assessment of the most reliable methods to estimate overdiagnosis .
We disagree with Chen and Duffy that considering age groups outside the screening age is unreliable. These data inform us about factors other than screening. Incidence of advanced cancers was strikingly similar among women offered screening and women below the screening age. Neoadjuvant therapy does not affect stage at diagnosis.
1. Jørgensen K, Gøtzsche P, Kalager M, Zahl P. Breast Cancer Screening in Denmark: A cohort study of tumor size and overdiagnosis. Ann Intern Med 2017;166:313-23.
2. Jørgensen KJ, Zahl PH, Gøtzsche PC. Breast cancer mortality in organised mammography screening in Denmark. A comparative study. BMJ 2010; 340:c1241.
3. Gøtzsche PC, Jørgensen KJ. Screening for breast cancer with mammography. Cochrane Database Syst Rev 2013, Issue 6. Art. No.: CD001877. DOI: 10.1002/14651858.CD001877.pub5.
4. Autier P, Boniol M, LaVecchia C, et al. Disparities in breast cancer mortality trends between 30 European countries: retrospective trend analysis of WHO mortality database. BMJ 2010;341:c3620.
5. Carter J, Coletti RJ, Harris RP. Quantifying and monitoring overdiagnosis in cancer screening: a systematic review of methods. BMJ 2015;50:g7773
Jørgensen KJ, Gøtzsche PC, Kalager M, Zahl P. Breast Cancer Screening in Denmark: A Cohort Study of Tumor Size and Overdiagnosis. Ann Intern Med. 2017;166:313–323. doi: 10.7326/M16-0270
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Published: Ann Intern Med. 2017;166(5):313-323.
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