Absolute numbers of lives saved and overdiagnosis in breast cancer screening, from a randomized trial and from the Breast Screening Programme in England
Duffy SW, Tabar L, Olsen AH, Vitak B et al
J Med Screen 2010;17:25-30
Link to Journal
Objectives: To estimate the absolute numbers of breast cancer deaths prevented and the absolute numbers of tumours over-diagnosed in mammographic screening for breast cancer at ages 50–69 years
Setting: The Swedish Two-County randomized trial of mammographic screening for breast cancer, and the UK Breast Screening Programme in England, ages 50–69 years
Methods: We estimated the absolute numbers of deaths avoided and additional cases diagnosed in the study group (active study population) of the Swedish Two-County Trial, by comparison with the control group (passive study population). We estimated the same quantities for the mortality and incidence rates in England (1974–2004 and 1974–2003, respectively). We used Poisson regression for statistical inference
Results: A substantial and significant reduction in breast cancer mortality was associated with screening in both the Two-County Trial (P < 0.001) and the screening programme in England (P < 0.001). The absolute benefits were estimated as 8.8 and 5.7 breast cancer deaths prevented per 1000 women screened for 20 years starting at age 50 from the Two-County Trial and screening programme in England, respectively. The corresponding estimated numbers of cases overdiagnosed per 1000 women screened for 20 years were, respectively, 4.3 and 2.3 per 1000.
Conclusions: The benefit of mammographic screening in terms of lives saved is greater in absolute terms than the harm in terms of overdiagnosis. Between 2 and 2.5 lives are saved for every overdiagnosed case
Thursday, 1 April 2010
Friday, 26 March 2010
New Gotzsche paper dismissing screening - this time in Denmark
In a paper published in the Research section of the BMJ today, Peter Gotzsche once again lines up the guns against organized screening programs, targeting in this instance the Danish Screening Program.
http://www.bmj.com/cgi/content/full/340/mar23_1/c1241
His conclusions are -
"We were unable to find an effect of the Danish screening programme on breast cancer mortality. The reductions in breast cancer mortality we observed in screening regions were similar or less than those in non-screened areas and in age groups too young to benefit from screening, and are more likely explained by changes in risk factors and improved treatment than by screening mammography
We believe it is time to question whether screening has delivered the promised effect on breast cancer mortality."
As this may hit mainstream news media, I have gathered some responses so far -
Danish and Swedish experts have replied saying that -
They claim that mammography screening in Denmark had no impact on breast cancer mortality. This claim is unsubstantiated, firstly because the authors used very crude data, and secondly because the analysis was not geared to answer the question.
Firstly, breast cancer screening can only possibly have an effect on women not already diagnosed with breast cancer prior to screening. Therefore the so-called “refined mortality” should be used in evaluation of screening. Jørgensen et al did not used refined mortality. Furthermore, they merge data from three screening areas starting screening at different points in time, and used age groups instead of cohorts. Together this gave quite “polluted” data.
Secondly, they calculated “annual change in the relative risk of breast cancer death” by time period and areas excluding 1992-1996. The relevant outcome measure is, however, the change in breast cancer mortality in the screening area controlled for the change in breast cancer mortality in the non-screening area.
Even using these “polluted” data, the relative breast cancer mortality decreased for women aged 55-74 covered by screening, while the relative breast cancer mortality did not decrease for women aged 35-54 largely uncovered by screening, and the relative breast cancer mortality was slightly but statistically non-significantly decreased for women aged 75-84 where the majority, but not all, of the person years were uncovered by screening. Although this pattern in the data is actually visible in Figure 1 in the paper by Jørgensen et al, it was missed in their analysis among other things because they excluded data from the period 1992-1996.
As we have reported previously, the measured impact of mammography screening on breast cancer mortality is highly dependent on the data set used for the analysis. Use of “polluted” data leads to biased estimates (2). Using cohort based refined mortality, we found a 25% decrease in breast cancer mortality in the municipality of Copenhagen during the first 10 years following the introduction of mammography screening in April 1991 (3). We deliberately did not include data from Funen and Frederiksberg in that analysis, as cause of death data were not available at that time for the first 10 years of these two screening programmes.
Other commentators also note -
The analysis of population trends in breast cancer mortality in the presence of screening is complicated by the inability to measure exposure to screening, and the long period of follow-up required. Studies such as this one by Jørgensen et al obscure whatever benefit may be present with crude, insensitive methodology. While we expect to see a range of benefits from mammography, some small and some large, based on the design and quality of the screening program, its duration, and the participation rate of the target population, to argue that there is no benefit from modern mammography on the basis of such flawed methods means this paper contributes nothing of substance to the on-going debate
http://www.bmj.com/cgi/content/full/340/mar23_1/c1241
His conclusions are -
"We were unable to find an effect of the Danish screening programme on breast cancer mortality. The reductions in breast cancer mortality we observed in screening regions were similar or less than those in non-screened areas and in age groups too young to benefit from screening, and are more likely explained by changes in risk factors and improved treatment than by screening mammography
We believe it is time to question whether screening has delivered the promised effect on breast cancer mortality."
As this may hit mainstream news media, I have gathered some responses so far -
Danish and Swedish experts have replied saying that -
They claim that mammography screening in Denmark had no impact on breast cancer mortality. This claim is unsubstantiated, firstly because the authors used very crude data, and secondly because the analysis was not geared to answer the question.
Firstly, breast cancer screening can only possibly have an effect on women not already diagnosed with breast cancer prior to screening. Therefore the so-called “refined mortality” should be used in evaluation of screening. Jørgensen et al did not used refined mortality. Furthermore, they merge data from three screening areas starting screening at different points in time, and used age groups instead of cohorts. Together this gave quite “polluted” data.
Secondly, they calculated “annual change in the relative risk of breast cancer death” by time period and areas excluding 1992-1996. The relevant outcome measure is, however, the change in breast cancer mortality in the screening area controlled for the change in breast cancer mortality in the non-screening area.
Even using these “polluted” data, the relative breast cancer mortality decreased for women aged 55-74 covered by screening, while the relative breast cancer mortality did not decrease for women aged 35-54 largely uncovered by screening, and the relative breast cancer mortality was slightly but statistically non-significantly decreased for women aged 75-84 where the majority, but not all, of the person years were uncovered by screening. Although this pattern in the data is actually visible in Figure 1 in the paper by Jørgensen et al, it was missed in their analysis among other things because they excluded data from the period 1992-1996.
As we have reported previously, the measured impact of mammography screening on breast cancer mortality is highly dependent on the data set used for the analysis. Use of “polluted” data leads to biased estimates (2). Using cohort based refined mortality, we found a 25% decrease in breast cancer mortality in the municipality of Copenhagen during the first 10 years following the introduction of mammography screening in April 1991 (3). We deliberately did not include data from Funen and Frederiksberg in that analysis, as cause of death data were not available at that time for the first 10 years of these two screening programmes.
Other commentators also note -
The analysis of population trends in breast cancer mortality in the presence of screening is complicated by the inability to measure exposure to screening, and the long period of follow-up required. Studies such as this one by Jørgensen et al obscure whatever benefit may be present with crude, insensitive methodology. While we expect to see a range of benefits from mammography, some small and some large, based on the design and quality of the screening program, its duration, and the participation rate of the target population, to argue that there is no benefit from modern mammography on the basis of such flawed methods means this paper contributes nothing of substance to the on-going debate
Tuesday, 16 March 2010
The US Preventive Services Task Force recommendations on Screening Mammography flawed
Guidelines for mammography screening published by the U.S. Preventive Services Task Force (USPSTF) in November not only are based on flawed methodology, they also fail to address current breast imaging practice and data, making them obsolete, according to a critique published in this month's Journal of Diagnostic Medical Sonography
Author Kevin Evans, Ph.D., evaluated the USPSTF's report methodology and found that it did not meet established standards for systematic reviews (JDMS, January/February 2010, Vol. 26:1, pp. 19-23). Evans is chair of the radiologic sciences division in the School of Allied Medical Professions at Ohio State University in Columbus.
Evans used two resources to evaluate the USPSTF's report: the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a 27-point checklist, and the Assessment of Multiple Systematic Reviews (AMSTAR), an 11-point checklist.
The task force's report scored 7 out of 27 on the PRISMA checklist and 1 out of 11 on the AMSTAR list. These low methodological scores put in question the rigor used in developing the report, limiting it to a review of literature instead of a formal systematic review and reducing its overall scientific impact to a much lower level in the hierarchy of evidence, according to Evans.
"I picked two of the most well-known methods to evaluate systematic reviews and applied them to the report," he told AuntMinnie.com. "It's possible that USPSTF met these standards but failed to provide their methodology in the report. This becomes problematic in reading their guidelines."
The USPSTF's intention was to update its 2002 report by using other systematic reviews, meta-analyses, recently published literature, and data from the Breast Cancer Surveillance Consortium from 2000 to 2005. In its guidelines, it proposed the following, according to Evans:
USPSTF used data from film-screen mammography in its report, rather than taking into consideration that digital mammography was developed to address film-screen's limitations and is in widespread use, according to Evans. In fact, one of the puzzling things about the USPSTF report is its lack of any reference to the American College of Radiology Imaging Network (ACRIN) Digital Mammographic Imaging Screening Trial (DMIST), conducted in 2005.
"USPSTF didn't make specific mention of DMIST," he said. "And yet they claim that more evidence is needed to provide a guideline about benefits and harms associated with digital mammography, instead of film-screen mammography."
"Other U.S. Preventive Services Task Force reports are routinely high quality," Evans said. "It's possible that the breast cancer screening task force did a good job but didn't spell out their methods. In any case, their report has created confusion for everyone, as well as our government officials."
If the U.S. Department of Health and Human Services had addressed the guidelines point by point, this confusion might have been put to rest earlier, Evans said.
"[After the guidelines were released], the Department of Health and Human Services responded by telling the public not to pay attention," he said. "They should have asked the USPSTF to provide an addendum with additional details on their review."
In the aftermath of the report's publication, USPSTF should take several steps to clear up the confusion, Evans wrote: It needs to provide an addendum that details its methodology, and if a systematic review as outlined by PRISMA or AMSTAR has not been conducted, it needs to be done.
"A revised set of guidelines is needed to assist patients in making the best decision about participating in screening breast examinations," he concluded.
Author Kevin Evans, Ph.D., evaluated the USPSTF's report methodology and found that it did not meet established standards for systematic reviews (JDMS, January/February 2010, Vol. 26:1, pp. 19-23). Evans is chair of the radiologic sciences division in the School of Allied Medical Professions at Ohio State University in Columbus.
Evans used two resources to evaluate the USPSTF's report: the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a 27-point checklist, and the Assessment of Multiple Systematic Reviews (AMSTAR), an 11-point checklist.
The task force's report scored 7 out of 27 on the PRISMA checklist and 1 out of 11 on the AMSTAR list. These low methodological scores put in question the rigor used in developing the report, limiting it to a review of literature instead of a formal systematic review and reducing its overall scientific impact to a much lower level in the hierarchy of evidence, according to Evans.
"I picked two of the most well-known methods to evaluate systematic reviews and applied them to the report," he told AuntMinnie.com. "It's possible that USPSTF met these standards but failed to provide their methodology in the report. This becomes problematic in reading their guidelines."
The USPSTF's intention was to update its 2002 report by using other systematic reviews, meta-analyses, recently published literature, and data from the Breast Cancer Surveillance Consortium from 2000 to 2005. In its guidelines, it proposed the following, according to Evans:
- Routine screening mammography in women ages 40 to 49 years should not be conducted; rather, this process should be biennial at ages 50 to 74 years.
- A lack of published evidence currently exists to provide a guideline for screening mammography for women older than 75 years of age.
- A lack of evidence exists for assessing the benefits and harms of using clinical breast examinations for women 40 years and older.
- Self breast examination is not recommended to be taught to women by clinicians, as it is not a sensitive technique and raises a woman's level of anxiety.
- A lack of published evidence currently exists to provide a guideline about benefits and harms associated with digital mammography or MRI instead of film-screen mammography.
USPSTF used data from film-screen mammography in its report, rather than taking into consideration that digital mammography was developed to address film-screen's limitations and is in widespread use, according to Evans. In fact, one of the puzzling things about the USPSTF report is its lack of any reference to the American College of Radiology Imaging Network (ACRIN) Digital Mammographic Imaging Screening Trial (DMIST), conducted in 2005.
"USPSTF didn't make specific mention of DMIST," he said. "And yet they claim that more evidence is needed to provide a guideline about benefits and harms associated with digital mammography, instead of film-screen mammography."
"Other U.S. Preventive Services Task Force reports are routinely high quality," Evans said. "It's possible that the breast cancer screening task force did a good job but didn't spell out their methods. In any case, their report has created confusion for everyone, as well as our government officials."
If the U.S. Department of Health and Human Services had addressed the guidelines point by point, this confusion might have been put to rest earlier, Evans said.
"[After the guidelines were released], the Department of Health and Human Services responded by telling the public not to pay attention," he said. "They should have asked the USPSTF to provide an addendum with additional details on their review."
In the aftermath of the report's publication, USPSTF should take several steps to clear up the confusion, Evans wrote: It needs to provide an addendum that details its methodology, and if a systematic review as outlined by PRISMA or AMSTAR has not been conducted, it needs to be done.
"A revised set of guidelines is needed to assist patients in making the best decision about participating in screening breast examinations," he concluded.
Monday, 16 November 2009
Breast Cancer Screening Guidelines Changing again
Furore in the colleges and societies, as the US preventive services task force releases it's new breast cancer screening guidelines, following the release of a paper in the Annals of Internal Medicine today
Their recommendations for starting screening at 50 (for women without a family history of breast cancer) with mammograms every 2 years, and ending at 74 years, more closely mimics the recommendations for screening in European countries, and broadly similar to the UK NHSBSP.
The task force is an independent panel of experts in prevention and primary care appointed by the federal Department of Health and Human Services.
The guidelines were published in today's (Nov 16, 2009) edition of the Annals of Internal Medicine
In order to formulate its guidelines, the task force used new data from mammography studies in England and Sweden and also commissioned six groups to make statistical models to analyze the aggregate data. The models were the only way to answer questions like how much extra benefit do women get if they are screened every year
Dr. Karla Kerlikowske, a professor in the department of medicine, epidemiology and biostatistics at the University of California, San Francisco said "The message for most women is to forgo routine mammograms if they are in their 40s.
Starting at age 50, Dr. Kerlikowske said, “the message is to get 10 mammograms in a lifetime, one every two years.” That way they get the most benefit and the least harm from the test. If women are healthy, she added, they might consider having mammograms every two years until age 74.
Nearly two-thirds of all women in their 40s had mammograms within the last two years, as did 72 percent of women age 50 to 65, according to an editorial by Dr. Kerlikowske that accompanies the report.
The Society of Breast Imaging and the American College of Radiology, the American Cancer Society, and many other respected professional organizations, have voiced strong opposition to the changes proposed in the articles.
It is the opinion of the SBI leadership that adopting these guidelines would result in a major step backward in women's healthcare and increased deaths from breast cancer.
Immediately, they provided a number of guidance documents and statements as follows (which is a model for speedy response to crises) -
STATEMENT FROM THE AMERICAN COLLEGE OF RADIOLOGY AND THE SOCIETY OF BREAST IMAGING:
USPSTF Mammography Recommendations Will Result in Unnecessary Breast Cancer Deaths Each Year
Talking Points in response to USPSTF Statement
Detailed ACR Statement on Ill Advised and Dangerous USPSTF Mammography Recommendations: Mammography Screening References
American Cancer Society Statement
Komen Screening Statement 11-16-09
NCI Statement
Thursday, 22 October 2009
Rethinking strategies for breast and prostate cancer screening
Twenty years of screening for breast and prostate cancer—the most diagnosed cancers for women and men—have not brought the anticipated decline in deaths from these diseases, argue experts in an opinion piece published Wednesday in the Journal of the American Medical Association
In an article published yesterday (Oct 21, 2009) in JAMA, Laura Esserman et al, one of our UCSF breast surgeons, and leader of the ATHENA project in the University of California, discuss whether we should be reconsidering looking at our screening tools for both breast and prostate cancer, and be more intelligent in their use.
"Screening does provide some benefit, but the problem is that the benefit is not nearly as much as we hoped and comes at the cost of over-diagnosis and over-treatment," said Laura Esserman, MD, professor of surgery and radiology, director of the University of California, San Francisco (UCSF) Carol Franc Buck Breast Care Center.
We acknowledge that screening is not perfect, as there are a proportion of women who are screened but would never die of the disease (lead time bias). Also there are the group of women who present as interval cancers due to their very different biology. These women still get their mammograms at the proscribed times, but tend to develop cancer between their screening tests.
"We need to focus on developing new tools to identify men and women at risk for the most aggressive cancers, to identify at the time of diagnosis those who have indolent or 'idle' tumors that are not life-threatening,"
Periodic screening may find some tumors early, but patients may not be screened often enough for lethal tumors to be detected in time to prevent death, leading the authors to conclude: "Without the ability to distinguish cancers that pose minimal risk from those posing substantial risk and with highly sensitive screening tests, there is an increased risk that the population will be over-treated."
The authors suggested that to improve screening, "a new focus is recommended for research and care to identify markers that discriminate minimal-risk from high-risk disease (and) identify less aggressive interventions for minimal-risk disease to reduce treatment burden for patients and society."
The authors made the following recommendations for early cancer detection and prevention:
- Develop tests to distinguish between low-risk and lethal cancers.
- Reduce treatment for low-risk disease. “Diagnosing cancers that don't kill the patient has led to treatment that may do more harm than good,” they wrote.
- Develop tools for physicians and patients to help them make informed decisions about prevention, screening, biopsy and treatment.
- Offer treatments individually tailored to a patient's tumor.
- Work to identify the people at highest risk for cancer and use proven preventive interventions.
This is a mix of researcher and clinicians who are trying to put research to clinical use (bench to bedside medicine)
Targeting screening tests to the at risk population may give better outcomes with fewer so called "false positives" from screening, thereby benefiting the screened women the most. It will also save us from overtreating some of the lower risk/indolent cancers that occur.
NCI commentary is available in their bulletin
Tuesday, 29 September 2009
CAD and Screening Mammography: ready for prime time?
In this months RADIOLOGY, Robyn Birdwell and Liane Philpotts share their different viewpoints on CAD and screening mammography. Both are well known mammographers in the North East, with Robyn being a guest of the RCR Breast Group at November's Annual Scientific Meeting
In the first of the two articles, Robyn Birdwell talks about the various CAD studies, and how the proponderance of data supports the use of CAD in screening mammography, and that "Having a system to aid the human eye that does nottake vacations, is not vulnerable to fatigue or environmental distractions, is without, emotion, and is designed specifically to assist the very human eye to "look over here" seems like a good idea"
The Preponderance of Evidence Supports Computer-aided Detection for Screening Mammography
Robyn L. Birdwell
Radiology 2009;253 9-16
http://radiology.rsna.org/cgi/content/full/253/1/9?etoc
In the second editorial article, Liane Philpotts points out that recalling patients from screening is sometimes more of an art than a science, and I am sure that many experienced radiologists would share her view.
One of the main issues with CAD is the necessary high false-positive rate of CAD prompts which subsequently means that the specificity is low, and we have the distracting factor of many false calls, while also knowing that not all cancers are picked up by CAD
Understanding of the limitations of computer-aided detection is important for those interpreting mammograms; this cautious approach to the use of computer-aided detection should help optimize this presently imperfect system and minimize the possible detrimental effects
Can Computer-aided Detection Be Detrimental to Mammographic Interpretation?
Liane E. Philpotts
Radiology 2009;253 17-22
http://radiology.rsna.org/cgi/content/full/253/1/17?etoc
In the first of the two articles, Robyn Birdwell talks about the various CAD studies, and how the proponderance of data supports the use of CAD in screening mammography, and that "Having a system to aid the human eye that does nottake vacations, is not vulnerable to fatigue or environmental distractions, is without, emotion, and is designed specifically to assist the very human eye to "look over here" seems like a good idea"
The Preponderance of Evidence Supports Computer-aided Detection for Screening Mammography
Robyn L. Birdwell
Radiology 2009;253 9-16
http://radiology.rsna.org/cgi/content/full/253/1/9?etoc
In the second editorial article, Liane Philpotts points out that recalling patients from screening is sometimes more of an art than a science, and I am sure that many experienced radiologists would share her view.
One of the main issues with CAD is the necessary high false-positive rate of CAD prompts which subsequently means that the specificity is low, and we have the distracting factor of many false calls, while also knowing that not all cancers are picked up by CAD
Understanding of the limitations of computer-aided detection is important for those interpreting mammograms; this cautious approach to the use of computer-aided detection should help optimize this presently imperfect system and minimize the possible detrimental effects
Can Computer-aided Detection Be Detrimental to Mammographic Interpretation?
Liane E. Philpotts
Radiology 2009;253 17-22
http://radiology.rsna.org/cgi/content/full/253/1/17?etoc
Monday, 14 September 2009
Informing patients about breast cancer screening - risks of overdiagnosis
A recent posting on the NHS National Prescribing Centre website blog addresses the issues of possible overdiagnosis of inconsequential cancers found as part of routine screening.
Blog link here
It is estimated that approximately 30% of breast cancers found at screening are of low grade and metastatic potential (low oncotype score) which may never kill the patient, and are therefore counted as being overdiagnosis.
Various tools are available to help primary care providers and others wishing to assist women to make informed decisions about whether to have screening or not.
Patient decision aids may help to guide women make the decision alongside the literature from the NHSBSP
Blog link here
It is estimated that approximately 30% of breast cancers found at screening are of low grade and metastatic potential (low oncotype score) which may never kill the patient, and are therefore counted as being overdiagnosis.
Various tools are available to help primary care providers and others wishing to assist women to make informed decisions about whether to have screening or not.
Patient decision aids may help to guide women make the decision alongside the literature from the NHSBSP
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