Overdiagnosis Of Invasive Breast Cancer Research Articles

Overdiagnosis of invasive breast cancer in population-based breast cancer screening: A short- and long-term perspective

BackgroundOverdiagnosis of invasive breast cancer (BC) is a contentious issue. ObjectiveThe aim of this paper is to estimate the overdiagnosis rate of invasive BC in an organised BC screening program and to evaluate the impact of age and follow-up time. MethodsThe micro-simulation model SiMRiSc was calibrated and validated for BC screening in Flanders, where women are screened biennially from age 50 to 69. Overdiagnosis rate was defined as the number of invasive BC that would not have been diagnosed in the absence of screening per 100,000 screened women during the screening period plus follow-up time (which was set at 5 years and varied from 2 to 15 years). Overdiagnosis rate was calculated overall and stratified by age. ResultsThe overall overdiagnosis rate for women screened biennially from 50 to 69 was 20.1 (95%CI: 16.9–23.2) per 100,000 women screened at 5-year follow-up from stopping screening. Overdiagnosis at 5-year follow-up time was 12.9 (95%CI: 4.6–21.1) and 74.2 (95%CI: 50.9–97.5) per 100,000 women screened for women who started screening at age 50 and 68, respectively. At 2- and 15-year follow-up time, overdiagnosis rate was 98.5 (95%CI: 75.8–121.3) and 13.4 (95%CI: 4.9–21.9), respectively, for women starting at age 50, and 297.0 (95%CI: 264.5–329.4) and 34.2 (95%CI: 17.5–50.8), respectively, for those starting at age 68. ConclusionsSufficient follow-up time (≥10 years) after screening stops is key to obtaining unbiased estimates of overdiagnosis. Overdiagnosis of invasive BC is a larger problem in older compared to younger women.

Benefits and harms of breast cancer screening with mammography in women aged 40–49 years: A systematic review

Early detection of breast cancer through screening can lower breast cancer mortality rates and reduce the burden of this disease in the population. In most western countries, mammography screening starting from age 50 is recommended. However, there is debate about whether breast cancer screening should be extended to younger women. This systematic review provides an overview of the evidence from RCTs on the benefits and harms of breast cancer screening with mammography in women aged 40-49 years. The quality of the evidence for each outcome was appraised using the GRADE approach. Four articles reporting on two different trials-the Age trial and the Canadian National Breast Screening Study-I (CNBSS-I)-were included. The results showed no significant effect on breast cancer mortality (Age trial: RR 0.93 (95% CI 0.80-1.09); CNBSS-I: HR 1.10 (95% CI 0.86-1.40)) nor on all-cause mortality (RR 0.98, 95% CI 0.93-1.03) in women aged 40-49 years offered screening. Among regularly attending women, the cumulative risk of experiencing a false-positive recall was 20.5%. Over-diagnosis of invasive breast cancer at 5years post-cessation of screening for women aged 40-49 years was estimated to be 32% and at 20 years post-cessation of screening to be 48%. Including ductal carcinoma in situ, these numbers were 41% and 55%. Based on the current evidence from randomised trials, extending mammography screening to younger age groups cannot be recommended. However, there were limitations including relatively low sensitivity of screening and screening attendance, insufficient power, and contamination, which may explain the nonsignificant results.

Revised estimates of overdiagnosis from the Canadian National Breast Screening Study

We have re-estimated overdiagnosis of breast cancer from mammography screening by age group in the Canadian National Breast Screening Study (CNBSS), a randomized screening trial. In the CNBSS, participants were recruited in 15 centers. 89,835 women were randomized with informed consent, 50,430 age 40–49 and 39,405 age 50–59. Women aged 40–49 received annual mammography and physical examination (MA+PX) versus a single physical examination and usual care in the community (UC). Women aged 50–59 received (MA+PX) versus (PX-alone) annually. Individual randomization resulted in 44 almost identically distributed demographic and risk factors. Annual compliance over the five or four scheduled screens was 86–95%. The cumulative numbers of invasive and in situ breast cancers ascertained by year during screening and subsequent follow-up to 25 years post entry to the CNBSS in the mammography arm have been compared to those in the control arm. Estimates of overdiagnosis were derived using post-screening cessation cut-off points from 1 to 20years.⋯Overdiagnosis of invasive breast cancer at five years post cessation of screening for women aged 40–49 was estimated to be 32%, and 16% for women aged 50–59; 20years post cessation of screening 48% for women 40–49 and 5% for those 50–59. Including ductal carcinoma in situ with invasive cancer, estimates were 41%, 25%, 55% and 16%, respectively. We conclude that approximately 30% of invasive screen-detected breast cancers in women age 40–49 were overdiagnosed, and 20% of those screen-detected in women age 50–59. Including ductal carcinoma in situ, the estimates are 40% and 30%, respectively.

Benefits and harms of mammography screening after age 74 years: model estimates of overdiagnosis.

The aim of this study was to quantify the benefits and harms of mammography screening after age 74 years, focusing on the amount of overdiagnosis of invasive breast cancer and ductal carcinoma in situ (DCIS). Three well-established microsimulation models were used to simulate a cohort of American women born in 1960. All women received biennial screening starting at age 50 years with cessation ages varying from 74 up to 96 years. We estimated the number of life-years gained (LYG), quality-adjusted life-years, breast cancer deaths averted, false-positives, and overdiagnosed women per 1000 screens. The models predicted that there were 7.8 to 11.4 LYG per 1000 screens at age 74 years (range across models), decreasing to 4.8 to 7.8 LYG per 1000 screens at age 80 years, and 1.4 to 2.4 LYG per 1000 screens at age 90 years. When adjusted for quality-of-life decrements, the LYG decreased by 5% to 13% at age 74 years and 11% to 22% at age 80 years. At age 90 to 92 years, all LYG were counterbalanced by a loss in quality-of-life, mainly because of the increasing number of overdiagnosed breast cancers per 1000 screens: 1.2 to 5.0 at age 74 years, 1.8 to 6.0 at age 80 years, and 3.7 to 7.5 at age 90 years. The age at which harms began to outweigh benefits shifted to a younger age when larger or longer utility losses because of a breast cancer diagnosis were assumed. The balance between screening benefits and harms becomes less favorable after age 74 years. At age 90 years, harms outweigh benefits, largely as a consequence of overdiagnosis. This age was the same across the three models, despite important model differences in assumptions on DCIS.

Overdiagnosis by mammographic screening for breast cancer studied in birth cohorts in The Netherlands.

A drawback of early detection of breast cancer through mammographic screening is the diagnosis of breast cancers that would never have become clinically detected. This phenomenon, called overdiagnosis, is ideally quantified from the breast cancer incidence of screened and unscreened cohorts of women with follow-up until death. Such cohorts do not exist, requiring other methods to estimate overdiagnosis. We are the first to quantify overdiagnosis from invasive breast cancer and ductal carcinoma in situ (DCIS) in birth cohorts using an age-period-cohort -model (APC-model) including variables for the initial and subsequent screening rounds and a 5-year period after leaving screening. Data on the female population and breast cancer incidence were obtained from Statistics Netherlands, "Stichting Medische registratie" and the Dutch Cancer Registry for women aged 0-99 years. Data on screening participation was obtained from the five regional screening organizations. Overdiagnosis was calculated from the excess breast cancer incidence in the screened group divided by the breast cancer incidence in presence of screening for women aged 20-99 years (population perspective) and for women in the screened-age range (individual perspective). Overdiagnosis of invasive breast cancer was 11% from the population perspective and 17% from the invited women perspective in birth cohorts screened from age 49 to 74. For invasive breast cancer and DCIS together, overdiagnosis was 14% from population perspective and 22% from invited women perspective. A major strength of an APC-model including the different phases of screening is that it allows to estimate overdiagnosis in birth cohorts, thereby preventing overestimation.

Mammography screening in Norway caused substantial overdiagnosis and did not reduce late-stage breast cancers

Commentary on: Kalager M , Adami HO, Bretthauer M, et al . Overdiagnosis of invasive breast cancer due to mammography screening: results from the Norwegian screening program. Ann Intern Med...

Overdiagnosis of Invasive Breast Cancer due to Mammography Screening

Letters7 August 2012Overdiagnosis of Invasive Breast Cancer due to Mammography ScreeningKarsten J. Jørgensen, MDKarsten J. Jørgensen, MDFrom The Nordic Cochrane Centre, 2100 Copenhagen, Denmark.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-157-3-201208070-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We estimated 37% overdiagnosis of invasive breast cancer in Norway and 52% when we included cases of ductal carcinoma in situ (DCIS) (1). This means that 1 in 3 cases of breast cancer detected in the screened age group is overdiagnosed. We estimated 33% overdiagnosis in Denmark (2), which has the longest period worldwide that allows a contemporaneous comparison between screened and nonscreened areas.There are 3 main reasons for the difference between our estimates for Norway and the estimated 18% to 25% overdiagnosis of invasive breast cancer in Kalager and colleagues' study (3). We prefer the ...

Overdiagnosis of Invasive Breast Cancer due to Mammography Screening

Letters7 August 2012Overdiagnosis of Invasive Breast Cancer due to Mammography ScreeningPer-Henrik Zahl, DrMedSciPer-Henrik Zahl, DrMedSciFrom Norwegian Institute of Public Health, N-0403 Oslo, Norway.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-157-3-201208070-00024 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Kalager and colleagues (1) reported a 15% to 25% overdiagnosis rate of invasive cancer in the Norwegian Breast Cancer Screening Program. In 2004, my coworkers and I reported (2) that screening led to a 51% increase in breast cancer cases that could not be explained by earlier diagnosis and called this increase overdiagnosis. We updated our study in 2012 (3) and reported the same high level of overdiagnosis. Our updated study had longer follow-up and included 11 631 breast cancer cases diagnosed after screening started, whereas Kalager and colleagues' analysis included only 3862 cases. The difference in estimates ...

Overdiagnosis of Invasive Breast Cancer due to Mammography Screening

Overdiagnosis of Invasive Breast Cancer due to Mammography Screening

Overdiagnosis of Invasive Breast Cancer due to Mammography Screening

Overdiagnosis of Invasive Breast Cancer due to Mammography Screening

Overdiagnosis of Invasive Breast Cancer due to Mammography Screening

Letters7 August 2012Overdiagnosis of Invasive Breast Cancer due to Mammography ScreeningMette Kalager, MD, Hans-Olov Adami, MD, PhD, Michael Bretthauer, MD, PhD, and Rulla M. Tamimi, ScDMette Kalager, MDFrom Harvard School of Public Health, Boston, MA 02115; Oslo University Hospital Rikshospitalet, N-0027 Oslo, Norway; and Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.Search for more papers by this author, Hans-Olov Adami, MD, PhDFrom Harvard School of Public Health, Boston, MA 02115; Oslo University Hospital Rikshospitalet, N-0027 Oslo, Norway; and Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.Search for more papers by this author, Michael Bretthauer, MD, PhDFrom Harvard School of Public Health, Boston, MA 02115; Oslo University Hospital Rikshospitalet, N-0027 Oslo, Norway; and Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.Search for more papers by this author, and Rulla M. Tamimi, ScDFrom Harvard School of Public Health, Boston, MA 02115; Oslo University Hospital Rikshospitalet, N-0027 Oslo, Norway; and Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-157-3-201208070-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Ms. Falk and colleagues state that the correct number of women invited to the screening program is 592 155. However, based on data provided to us by the Cancer Registry of Norway, approximately 496 157 women were invited to the screening program in our study period. Furthermore, they may have misunderstood our estimates of overdiagnosis, which were based on 4 groups of women, comparing current with historical groups. The actual number of invited women is not included in any of our estimates. As shown in our article, we estimated the number of overdiagnosed women as the number of women with ...

Overdiagnosis of Invasive Breast Cancer with Screening Mammography

Much attention has been focused on overdiagnosis when screening for prostate cancer, but how common is overdiagnosis with screening mammography? In

Overdiagnosis of Invasive Breast Cancer With Mammography Screening

Overdiagnosis of Invasive Breast Cancer With Mammography Screening

Overdiagnosis of Invasive Breast Cancer Due to Mammography Screening: Results From the Norwegian Screening Program

Precise quantification of overdiagnosis of breast cancer (defined as the percentage of cases of cancer that would not have become clinically apparent in a woman's lifetime without screening) due to mammography screening has been hampered by lack of valid comparison groups that identify incidence trends attributable to screening versus those due to temporal trends in incidence. To estimate the percentage of overdiagnosis of breast cancer attributable to mammography screening. Comparison of invasive breast cancer incidence with and without screening. A nationwide mammography screening program in Norway (inviting women aged 50 to 69 years), gradually implemented from 1996 to 2005. The Norwegian female population. Concomitant incidence of invasive breast cancer from 1996 to 2005 in counties where the screening program was implemented compared with that in counties where the program was not yet implemented. To adjust for changes in temporal trends in breast cancer incidence, incidence rates during the preceding decade were also examined. The percentage of overdiagnosis was calculated by accounting for the expected decrease in incidence following cessation of screening after age 69 years (approach 1) and by comparing incidence in the current screening group with incidence among women 2 and 5 years older in the historical screening groups, accounting for average lead time (approach 2). A total of 39,888 patients with invasive breast cancer were included, 7793 of whom were diagnosed after the screening program started. The estimated rate of overdiagnosis attributable to the program was 18% to 25% (P < 0.001) for approach 1 and 15% to 20% (P < 0.001) for approach 2. Thus, 15% to 25% of cases of cancer are overdiagnosed, translating to 6 to 10 women overdiagnosed for every 2500 women invited. The study was registry-based. Mammography screening entails a substantial amount of overdiagnosis. Norwegian Research Council and Frontier Science.

Controversies in Cancer Screening: Focusing on Colorectal Cancer Recommendations

Screening recommendations for common malignancies, such as cervical, breast, and prostate cancer, have been ques­ tioned in the past year, and vigorous professional, public, and private debates have ensued. For breast cancer screen­ ing, mammography recommendations have been rethought, most notably by the U.S. Preventive Services Task Force. Their recommendations support the use of mammography, but changes have been suggested regarding the ages to begin and end screening, as well as the frequency of the screening studies. Whereas for breast cancer very few have questioned a benefit of mammography in the appropriate population and situation (however, for opposing viewpoints, see Zahl et al), the case is different regarding prostate cancer screen­ ing. The use of prostate­specific antigen as a screening tool has been studied and found to be of questionable benefit. In certain clinical situations it might even lead to more harm than benefit. A fourth group of malignancies for which scree­ ning procedures are commonly used is colorectal cancers. Most physicians consider that colorectal cancer screening is beneficial and underutilized. Recent articles have discussed this underutilization, but have also noted that in various clinical scenarios, there is, surprisingly, inappropriate and over utilization, particularly regarding colonoscopies. For instance, the U.S. Preventive Services Task Force has issued guidelines for appropriate follow­up colonoscopic surveil­ lance after initial colonoscopy, including addressing when the initial exam reveals polyps. Despite these guidelines, it is common clinical practice to perform follow­up colonos­ copies more frequently and at shorter intervals than those recommended by expert committees. The controversies over breast and prostate cancer screen­ ings have highlighted a paradox: Inappropriate and overuse of screening tests can lead to adverse consequences, as well as incurring significant financial costs (thereby reducing financial resources that can be used for other important medical needs). Far beyond patients experiencing anxiety due to a large number of false positive screening studies, patients undergo considerable noninvasive and invasive testing, and a substantial number of patients are even treated for malignancies that would never impact on the quality or length of their lives. This unnecessary treatment scenario is widely recognized with prostate cancer, where patients undergo major procedures, not infrequently leading to incontinence and sexual dysfunction, for malignancies that would never progress in their lifetime. This is also true, though not as well known, for breast cancer. It is commonly known, exp­ ected and accepted that a percentage of patients will have an abnormal mammogram that will lead to further proce­ dures, including biopsies, which will ultimately rule out an invasive malignancy. Though this is known, it is enlighten­ ing to appreciate the frequency with which this occurs. Varying slightly with the age of the woman, if 1000 women were screened biennially for 10 years, approximately 200 will have an abnormal mammogram, and 60 will eventually have a biopsy. What isn’t as well known is that beyond the diagnosis and recognized conundrum of ductal carcinoma in situ, a clinical situation that will not progress to invasive breast cancer in most women, there is also a substantial overdiagnosis of invasive breast cancer, which then leads to treatment, including some combination of breast sur­ gery, radiation therapy, chemotherapy, and hormonal therapy. Though it seems counterintuitive and far beyond what one would expect, this overdiagnosis and subsequent treatment has been calculated to be as high as 30% to 40% of all the invasive breast cancers diagnosed. Balancing these nega­ tive consequences of screening mammography, it is esti mated that the number of lives saved for every 1000 women screened for 10 years is (age 40­50 years) 0.5 women, (age 50­60 years) 2 women, (age 60­70 years) 3 women, (age 70­80 years) 2 women. Screening controversies have arisen primarily due to the natural biological processes of these malignancies, which were not well appreciated until recently. Screening, as presently practiced, is based on the assumption that tumors, when small, are localized, and that if they are not removed while still small, they eventually grow and metastasize. Therefore, it is postulated that if they are discovered early, this metastatic spread can be prevented. However, it has become clear that not only do some tumors,

Estimates of overdiagnosis of invasive breast cancer associated with screening mammography

To estimate the extent of overdiagnosis of invasive breast cancer associated with screening in New South Wales, Australia, a population with a well-established mammography screening program which has achieved full geographic coverage. We calculated overdiagnosis as the observed annual incidence of invasive breast cancer in NSW in 1999-2001 (a screened population) minus the expected annual incidence in this population at the same time, as a percentage of the expected incidence. We estimated expected incidence without screening in 1999-2001 from the incidence of invasive breast cancer in: (1) women in unscreened age groups (interpolation method); and (2) women in all age groups prior to the implementation of screening (extrapolation method). We then adjusted these estimates for trends in major risk factors for breast cancer that may have coincided with the introduction of mammography screening: increasing obesity, use of hormone replacement therapy (HRT) and nulliparity. Finally, we adjusted for lead time to produce estimates of expected incidence in 1999-2001. These were compared with the observed incidence in 1999-2001 to calculate overdiagnosis of breast cancer associated with screening. Overdiagnosis of invasive breast cancer among 50-69 year NSW women was estimated to be 42 and 30% using the interpolation and extrapolation methods, respectively. Overdiagnosis of invasive breast cancer attributable to mammography screening appears to be substantial. Our estimates are similar to recent estimates from other screening programmes. Overdiagnosis merits greater attention in research and in clinical and public health policy making.

Estimation of lead time and overdiagnosis in breast cancer screening

Sir, It is reported that 7 years after the start of screening in Sweden, the incidence of invasive breast cancer in the screened age group was 69% higher than expected (Duffy et al, 2008). After adjustment for a lead time of 2.4 years and for the increased use of hormone replacement therapy, they found 39% excess. We have reservations about adjustments for lead time (Zahl et al, 2008). Correction for lead time should only be done for those cancers that would have been diagnosed at a later time in the absence of screening. But many screen-detected cancers would not have come to the women’s attention in their remaining lifetime, if they had not attended screening and are by definition overdiagnosed. If these cancers are not excluded from the calculation of lead time, the lead-time distribution will be artificially rightskewed, and the average lead time will appear to be much longer than it really is. Duffy et al, (2008) did not exclude such cancers from the calculation of lead time, but counted all excess cancers detected in a randomised trial as advanced diagnoses, when some of them were in fact overdiagnosed cases. They have therefore overestimated the lead-time effect. Duffy et al (2008) recognise that the detection of non-overdiagnosed cancers should give rise to a drop in incidence when the women leave the screening programme. Quantifying such a compensatory drop is a less bias-prone method for adjusting the incidence increase for leadtime effects, as it makes no assumption about the average lead time. It is also very simple to use (see, e.g., Zahl et al, 2004). We have done a systematic review of incidence trends in countries with organised mammography screening that presented data on breast cancer incidence for both screened and nonscreened age groups for at least 7 years before screening and 7 years after screening had been fully implemented (Jorgensen and Gotzsche, 2008). We were able to include data from United Kingdom, Canada, Australia, Sweden and Norway. We found that compensatory drops in the older age groups were small or absent, although major drops would have been expected if the lead time of 2.4 years were true. When we adjusted for these drops, we found 36% overdiagnosis of invasive breast cancer, in good agreement with the results of Duffy et al (2008), and 51% when we included carcinoma in situ. Duffy et al (2008) mention that after prolonged follow-up of the Malmo randomised screening trial, an overdiagnosis of 7–8% was reported and they find this estimate considerably more plausible than their own estimate of 39%. However, they have overlooked that the former estimate is seriously flawed (Zahl et al, 2008). There was substantial opportunistic screening in the control group and after adjustment for this, the overdiagnosis estimate in the Malmo trial is 24% (Gotzsche and Jorgensen, 2006). It is asserted that after adjustments, overdiagnosis estimates will be smaller than many rates quoted in the past (Duffy et al, 2008). We disagree, as most ‘rates quoted in the past’ have been too small (Gotzsche and Nielsen, 2006). On the basis of randomised trials, the overdiagnosis is 30% (Gotzsche and Nielsen, 2006), and it becomes 44% if adjusted for opportunistic screening in the control groups (Jorgensen and Gotzsche, 2008). The low rates in the past have been too low for the very reason that they have been based on flawed lead-time models (Jorgensen and Gotzsche, 2008; Zahl et al, 2008). We believe the most reliable estimate for organised mammography screening is 51% (Jorgensen and Gotzsche, 2008). This means that one in three breast cancers detected in a population offered organised mammography screening are overdiagnosed. Many women are therefore harmed substantially by screening, as practically all detected carcinoma in situ cases and invasive cancers are treated, at great physical and psychological costs.

Breast cancer incidence after the introduction of mammography screening

A prevalence peak is expected in breast cancer incidence when mammography screening begins, but afterward the incidence still may be elevated compared with prescreening levels. It is important to determine whether this is due to overdiagnosis (ie, the detection of asymptomatic disease that would otherwise not have arisen clinically). In the current study, the authors examined breast cancer incidence after the introduction of mammography screening in Denmark. Denmark has 2 regional screening programs targeting women ages 50 years to 69 years. The programs were initiated in 1991 and 1993, respectively. No screening takes place in the 13 other Danish regions. Data regarding incident breast cancers detected between 1979 and 2001 were retrieved from the Danish Cancer Registry for each screening region and for the rest of Denmark, and time trends in rates for women ages 50 years to 69 years were compared. From 1 program, individual screening data were used to analyze breast cancer incidence in women who were never screened, those who were screened for the first time, or those who previously were screened. The incidence of breast cancer was found to have increased regardless of screening. In the screening regions, a marked prevalence peak was observed, and the incidence hereafter was compatible with the level indicated by the 95% confidence limits for the regression curves for the rates in the prescreening period, taking into account the artificial ageing in the program, the influx of newcomers, and variations in the data. Women who had undergone previous screening were found to have the same incidence of breast cancer as women who were never screened. The data from the current study do not provide evidence of overdiagnosis of invasive breast cancer in the 2 Danish screening programs or, if overdiagnosis was found to occur, it was only of limited magnitude.