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The harms and benefits of modern screening mammography Women need more balanced information

DOI:10.1136/bmj.g3824
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Joann G Elmore at University of Washington Seattle
Joann G Elmore
Russell P Harris
Russell P Harris
Russell P Harris
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Abstract

Women need more balanced information The Swiss Medical Board, an independent health technology assessment consortium, recently reviewed the evidence for breast cancer screening and made recommendations to its government. The board noted that the current debate on the benefits and harms of mammography screening is based on outdated randomised controlled trials (RCTs) and that it was “non-obvious” that the benefits outweighed the harms.1 They recommended that no new mammography screening programmes should be introduced in Switzerland and that the existing ones should be phased out.1 The Swiss Medical Board relied on a review by another panel: the Independent United Kingdom Panel on Breast Cancer Screening.2 Using data from the published RCTs, the UK panel estimated that for every 10 000 women aged 50 invited to screen for the next 20 years, about 43 would avoid a death from breast cancer and the remaining 9957 would receive no mortality benefit. About 129 women would be treated unnecessarily as a result of overdiagnosis, a ratio of three women with overdiagnosed cancers to one woman with a breast cancer death avoided. As both panels noted, data from older RCTs are not ideal for determining the benefits and harms of modern day screening. Instead, observational studies such …
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The harms and benefits of modern screening
mammography
Women need more balanced information
Joann G Elmore professor of medicine 1, Russell P Harris professor of medicine 2
1Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA; 2Department of Medicine, University of North Carolina,
Chapel Hill, NC, USA
The Swiss Medical Board, an independent health technology
assessment consortium, recently reviewed the evidence for
breast cancer screening and made recommendations to its
government. The board noted that the current debate on the
benefits and harms of mammography screening is based on
outdated randomised controlled trials (RCTs) and that it was
“non-obvious” that the benefits outweighed the harms.1They
recommended that no new mammography screening
programmes should be introduced in Switzerland and that the
existing ones should be phased out.1
The Swiss Medical Board relied on a review by another panel:
the Independent United Kingdom Panel on Breast Cancer
Screening.2Using data from the published RCTs, the UK panel
estimated that for every 10 000 women aged 50 invited to screen
for the next 20 years, about 43 would avoid a death from breast
cancer and the remaining 9957 would receive no mortality
benefit. About 129 women would be treated unnecessarily as a
result of overdiagnosis, a ratio of three women with
overdiagnosed cancers to one woman with a breast cancer death
avoided.
As both panels noted, data from older RCTs are not ideal for
determining the benefits and harms of modern day screening.
Instead, observational studies such as in the linked paper (doi:10.
1136/bmj.g3701) will be increasingly relied on to monitor
changes over time.3
Much has changed since women were first enrolled into the
breast cancer screening RCTs, one of which started 50 years
ago, including factors that influence the incidence of breast
cancer (for example, postmenopausal hormone therapy and
increased obesity) or the timing of diagnosis (for example,
improved mammography technology and increased breast cancer
awareness). Most importantly, breast cancer treatment has
noticeably improved, and this may partially explain some of
the benefit attributed to mammography. Recent findings from
the 25 year follow-up of the Canadian National Breast Screening
Study underscore uncertainties about the applicability of the
older RCTs to current screening policies. That study showed
no benefit from screening, perhaps partly due to participants
receiving more effective treatment than in the older RCTs.4
Some commentators have asked for new trials, but results would
take decades and it would still be questioned whether further
changes in risk factors, treatment, and technology over these
decades had made the RCT results obsolete.
The new cohort study from Norway3adds important information
to a growing body of observational evidence estimating the
benefits and harms of screening. The authors followed women
for more than two decades during a time when the country’s
breast cancer screening programme was gradually implemented.
They found that, for every 10 000 women screened, about 27
deaths from breast cancer might be avoided.
Although observational studies may provide more up to date
estimates than the old RCTs, they also come with considerable
uncertainty. As these studies compare groups in different periods
(before and after screening programmes begin) or in different
geographical areas (with and without screening programmes),
they are susceptible to selection bias.5It is not surprising that
observational studies in Norway and other Scandinavian
countries have disagreed about the estimated mortality benefit
of screening mammography.6789The benefit reported in the
present study falls near the middle of these other published
estimates.
Overall, evidence from both observational studies and RCTs
indicates a benefit from screening mammography. Interestingly,
the estimates from the observational studies do not differ greatly
from those of the older RCTs: for every 10 000 women screened
over 20 years, an estimated 27 versus 43 women, respectively,
would avoid a breast cancer death. The Norwegian study largely
confirms what is already known: the benefits of screening
mammography are modest at best. While the benefits are small,
the harms of screening are real and include overdiagnosis,
psychological stress, and exorbitant healthcare costs.
So how can women be helped to make informed decisions about
screening? Unfortunately they are rarely presented with balanced
information. While the results of complex, imperfect science
Correspondence to: J G Elmore jelmore@u.washington.edu
For personal use only: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe
BMJ 2014;348:g3824 doi: 10.1136/bmj.g3824 (Published 17 June 2014) Page 1 of 2
Editorials
EDITORIALS
do not easily translate into memorable slogans, campaigns to
promote mammography do often catch women’s attention. Many
individuals and groups actively promote mammography
screening. Doctors discussing mammography with patients are
more likely to mention the potential benefits than harms of
screening.10 One US hospital promotes monthly “mingle and
mammograms” parties, with women being pampered before
screening to calm their nerves.11 These parties include appetizers,
foot massages, and bags emblazoned with the logo “fight like
a girl.” In addition to appetizers, we suggest serving women
balanced information about the benefits and harms of screening
to chew on.
Concern about the amount and type of information on screening
mammography made available to women is increasing
internationally. In the United Kingdom, concerns about women
receiving inadequate information when participating in their
national screening programme led to the formation of a special
“citizen’s jury” of women to review the issue.12 13 After hearing
evidence from experts, the jurors made recommendations on
the best way to present information on the benefits and harms
of mammography. Based on this experience, one participant
remarked: “I can’t believe how much I didn’t know.”14
Beyond its relevance to women’s decision making today, the
Norwegian study should make us reflect on how to monitor the
changing benefits and harms of breast cancer screening. Future
studies will hopefully allow analyses to account for changes
over time in risk factors, screening technology, and treatment.
Just as quality criteria have been defined for RCTs, creative
study methods and quality metrics must be developed for
observational studies evaluating large screening programmes.
For future independent boards to be able to conclude that the
breast cancer screening decision has finally become obvious,
careful assessment of ongoing screening programmes will be
required. In the meantime, make yourself comfortable—this
may take a while.
Competing interests: We have read and understood the BMJ Group
policy on declaration of interests and declare the following interests:
JGE serves as a medical editor for the non-profit Informed Medical
Decisions Foundation. RPH is a former member of the US Preventive
Services Task Force that makes national recommendations on
preventive care, including breast cancer screening.
Provenance and peer review: Commissioned; not externally peer
reviewed.
1 Biller-Andorno N, Jüni P. Abolishing mammography screening programs? A view from
the Swiss Medical Board. N Engl J Med 2014;370:1965-7.
2 Independent UK Panel on Breast Cancer Screening. The benefits and harms of breast
cancer screening: an independent review. Lancet 2012;380:1778-86.
3 Weedon-Fekjaer H, Romundstad P, Vatten LJ. Modern mammography screening and
breast cancer mortality: population study. BMJ 2014;348:g3701.
4Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA. Twenty five year follow-up for breast
cancer incidence and mortality of the Canadian National Breast Screening Study:
randomised screening trial. BMJ 2014;348:g366.
5 Harris R, Yeatts J, Kinsinger L. Breast cancer screening for women aged 50 to 69 years:
a systematic review of observational evidence. Prev Med 2011;53:108-14.
6 Kalager M, Zelen M, Langmark F, Adami H-O. Effect of screening mammography on
breast-cancer mortality in Norway. N Engl J Med 2010;363:1203-10.
7 Olsen AH, Lynge E, Njor SH, Kumle M, Waaseth M, Braaten T, et al. Breast cancer
mortality in Norway after the introduction of mammography screening. Int J Cancer
2013;132:208-14.
8 Hofvind S, Ursin G, Tretli S, Sebuødegård S, Møller B. Breast cancer mortality in
participants of the Norwegian Breast Cancer Screening Program. Cancer
2013;119:3106-12.
9 Kalager M, Loberg M, Bretthauer M, Adami HO. Comparative analysis of breast cancer
mortality following mammography screening in Denmark and Norway. Ann Oncol
2014;25:1137-43.
10 Hoffman RM, Lewis CL, Pignone MP, Couper MP, Barry MJ, Elmore JG, et al.
Decision-making processes for breast, colorectal, and prostate cancer screening: the
DECISIONS survey. Med Decis Making 2010;30(5 Suppl):S53S-64.
11 Ferraro N. Hastings hospital’s mammogram parties offer women a dose of pampering to
calm the nerves. St Paul Pioneer Press. 2011 Jan 20.
12 Hawkes N. “Citizens’ jury” disagrees over whether screening leaflet should put reassurance
before accuracy. BMJ 2012;345:e8047.
13 Hawkes N. Women “jurors” are asked how to present risk-benefit ratio of breast cancer
screening. BMJ 2012;345:e7886.
14 Coulter A. UK citizen’s jury advises on communication about the benefits and harms of
breast screening. Guest blog posted by Gary Schwitzer, 2013. www.healthnewsrevieworg.
Cite this as: BMJ 2014;348:g3824
© BMJ Publishing Group Ltd 2014
For personal use only: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe
BMJ 2014;348:g3824 doi: 10.1136/bmj.g3824 (Published 17 June 2014) Page 2 of 2
EDITORIALS
... Benefits of screening in older adults include patient satisfaction 32 and improved self-esteem. 14,24 Cancer screening, however, may also cause patient harms, including pain and anxiety during and/or in preparation for the test (e.g., bowel preparation for colonoscopy), 33 complications from the screening test itself (e.g., hospitalization for dehydration, bleeding, perforation after a colonoscopy) or from diagnostic tests following an abnormal finding (e.g., breast biopsy, removal of precursor lesion or bronchoscopy), 34 reassurance from false-negative tests, 35 and overdiagnosis of tumors that are of no threat. 33 All complications may increase with age. ...
... 14,24 Cancer screening, however, may also cause patient harms, including pain and anxiety during and/or in preparation for the test (e.g., bowel preparation for colonoscopy), 33 complications from the screening test itself (e.g., hospitalization for dehydration, bleeding, perforation after a colonoscopy) or from diagnostic tests following an abnormal finding (e.g., breast biopsy, removal of precursor lesion or bronchoscopy), 34 reassurance from false-negative tests, 35 and overdiagnosis of tumors that are of no threat. 33 All complications may increase with age. 33,35 Clinician. ...
... 33 All complications may increase with age. 33,35 Clinician. Outcomes are tied to whether the decision is in keeping with current guidelines, which are currently limited to age-based recommendations for breast and colon cancers. ...
An Individualized Approach to Cancer Screening Decisions in Older Adults: A Multilevel Framework
Article
Full-text available
Guidelines for optimal cancer screening in older adults remain unclear, particularly for adults over the age of 75. While cancer screening in older adults may benefit some in good health, it may cause unnecessary burdens in others with limited life expectancy. Thus, a systematic approach to enable individualized cancer screening decisions in older adults is needed. We suggest a framework that guides such decisions through evidence-based approaches from multiple interactions, and that involves the patient, clinician, and healthcare system. An individualized approach considers differences in disease risk rather than the chronological age of the patient. This paper presents a comprehensive framework that depicts the independent and converging levels of influences on individualized cancer screening decisions in older adults. This Individualized Decisions for Screening (IDS) framework recognizes the reality of these interrelationships, including the tensions that arise when behaviors and outcomes are valued differently at the patient, clinician, and healthcare organization levels. Person-centered approaches are essential to advancing multilevel research of individualized cancer screening decisions among older adults.
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... [7][8][9][10][11] Concerns about challenges interpreting these biopsy specimens lead many to obtain second opinions before initiating treatment. [12][13][14] While established diagnostic criteria exist to guide pathologists in breast tissue interpretation, the extent of disagreement among pathologists on diagnoses of atypia led us to question the reproducibility of the diagnoses. 15,16 That is, would pathologists diagnose atypia on a case they had previously interpreted as such? ...
... The addition of immunohistochemical stains improves the agreement rate and decreases atypia diagnoses in favor of usual hyperplasia, which would decrease surgical intervention for these lesions. 17,22 Our (7) radial scar/complex sclerosing lesion, (8) flat epithelial atypia, (9) intraductal papilloma with atypia, (10) atypical lobular hyperplasia, (11) atypical ductal hyperplasia, (12) lobular carcinoma-in-situ, (13) ductal carcinoma-in-situ, (14) invasive breast carcinoma study presents intraobserver data on a much larger sample of pathologists who work in multiple geographic areas of the United States, but our methods did not incorporate the option of additional diagnostic test results such as immunohistochemical stains, which might improve observed agreement for atypia. The statistically significant relationship between intraobserver agreement and fewer diagnoses for a case probably reflects epithelial complexity or overlapping diagnostic features (diagnostic distraction). ...
Diagnostic Reproducibility: What Happens When the Same Pathologist Interprets the Same Breast Biopsy Specimen at Two Points in Time?
Article
  • Dec 2016
Background Surgeons may receive a different diagnosis when a breast biopsy is interpreted by a second pathologist. The extent to which diagnostic agreement by the same pathologist varies at two time points is unknown. Methods Pathologists from eight U.S. states independently interpreted 60 breast specimens, one glass slide per case, on two occasions separated by ≥9 months. Reproducibility was assessed by comparing interpretations between the two time points; associations between reproducibility (intraobserver agreement rates); and characteristics of pathologists and cases were determined and also compared with interobserver agreement of baseline interpretations. ResultsSixty-five percent of invited, responding pathologists were eligible and consented; 49 interpreted glass slides in both study phases, resulting in 2940 interpretations. Intraobserver agreement rates between the two phases were 92% [95% confidence interval (CI) 88–95] for invasive breast cancer, 84% (95% CI 81–87) for ductal carcinoma-in-situ, 53% (95% CI 47–59) for atypia, and 84% (95% CI 81–86) for benign without atypia. When comparing all study participants’ case interpretations at baseline, interobserver agreement rates were 89% (95% CI 84–92) for invasive cancer, 79% (95% CI 76–81) for ductal carcinoma-in-situ, 43% (95% CI 41–45) for atypia, and 77% (95% CI 74–79) for benign without atypia. Conclusions Interpretive agreement between two time points by the same individual pathologist was low for atypia and was similar to observed rates of agreement for atypia between different pathologists. Physicians and patients should be aware of the diagnostic challenges associated with a breast biopsy diagnosis of atypia when considering treatment and surveillance decisions.
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... Unfortunately, the 20 years of followup needed to reliably observe mortality reductions attributable to screening (17) presents a problem of timing that no trial can circumvent. Treatments administered in a new trial may be outdated in 20 years (18). Moreover, predicting how treatment advances will affect screening is difficult. ...
The Effect of Treatment Advances on the Mortality Results of Breast Cancer Screening Trials: A Microsimulation Model
Article
Background: Mammography trials, which are the primary sources of evidence for screening benefit, were conducted decades ago. Whether advances in systemic therapies have rendered previously observed benefits of screening less significant is unknown. Objective: To compare the outcomes of breast cancer screening trials had they been conducted using contemporary systemic treatments with outcomes of trials conducted with previously used treatments. Design: Computer simulation model of 3 virtual screening trials with similar reductions in advanced-stage cancer cases but reflecting treatment patterns in 1975 (prechemotherapy era), 1999, or 2015 (treatment according to receptor status). Data sources: Meta-analyses of screening and treatment trials; study of dissemination of primary systemic treatments; SEER (Surveillance, Epidemiology, and End Results) registry. Target population: U.S. women aged 50 to 74 years. Time horizon: 10 and 25 years. Perspective: Population. Intervention: Mammography, chemotherapy, tamoxifen, aromatase inhibitors, and trastuzumab. Outcome measures: Breast cancer mortality rate ratio (MRR) and absolute risk reduction (ARR) obtained by the difference in cumulative breast cancer mortality between control and screening groups. Results of base-case analysis: At 10 years, screening in a 1975 trial yielded an MRR of 90% and an ARR of 5 deaths per 10 000 women. A 2015 screening trial yielded a 10-year MRR of 90% and an ARR of 3 deaths per 10 000 women. Results of sensitivity analysis: Greater reductions in advanced-stage disease yielded a greater screening effect, but MRRs remained similar across trials. However, ARRs were consistently lower under contemporary treatments. When contemporary treatments were available only for early-stage cases, the MRR was 88%. Limitation: Disease models simplify reality and cannot capture all breast cancer subtypes. Conclusion: Advances in systemic therapies for breast cancer have not substantively reduced the relative benefits of screening but have likely reduced the absolute benefits because of their positive effect on breast cancer survival. Primary funding source: University of Washington and National Cancer Institute.
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... More information is also needed on consumer knowledge of and willingness to risk overdiagnosis (67). Overall, this study has several important strengths, including collaboration of 6 long-established, independent modeling groups; use of well-calibrated models that reproduce temporal epidemiologic trends and a screening trial result; inclusion of digital technology; incorporation of increasingly effective treatments; and consideration of quality of life, risk factors, breast density, and comorbidity (68). The conclusions about the ranking of screening strategies are robust and should provide greater credibility than inferences based on 1 model alone. ...
Collaborative Modeling of the Benefits and Harms Associated With Different U.S. Breast Cancer Screening Strategies
Article
Full-text available
Background: Controversy persists about optimal mammography screening strategies. Objective: To evaluate screening outcomes, taking into account advances in mammography and treatment of breast cancer. Design: Collaboration of 6 simulation models using national data on incidence, digital mammography performance, treatment effects, and other-cause mortality. Setting: United States. Patients: Average-risk US female population and subgroups with varying risk, breast density, or comorbidity. Intervention: Eight strategies differing by age at which screening starts (40, 45, or 50 years) and screening interval (annual, biennial, and hybrid [annual for women in their 40s and biennial thereafter]). All strategies assumed 100% adherence and stopped at age 74 years. Measurements: Benefits (breast cancer-specific mortality reduction, breast cancer deaths averted, life-years, and quality-adjusted life-years); number of mammograms used; harms (false-positive results, benign biopsies, and overdiagnosis); and ratios of harms (or use) and benefits (efficiency) per 1000 screens. Results: Biennial strategies were consistently the most efficient for average-risk women. Biennial screening from age 50 to 74 years avoided a median of 7 breast cancer deaths versus no screening; annual screening from age 40 to 74 years avoided an additional 3 deaths, but yielded 1988 more false-positive results and 11 more overdiagnoses per 1000 women screened. Annual screening from age 50 to 74 years was inefficient (similar benefits, but more harms than other strategies). For groups with a 2- to 4-fold increased risk, annual screening from age 40 years had similar harms and benefits as screening average-risk women biennially from 50 to 74 years. For groups with moderate or severe comorbidity, screening could stop at age 66 to 68 years. Limitation: Other imaging technologies, polygenic risk, and nonadherence were not considered. Conclusion: Biennial screening for breast cancer is efficient for average-risk populations. Decisions about starting ages and intervals will depend on population characteristics and the decision makers' weight given to the harms and benefits of screening. Primary funding source: National Institutes of Health.
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... So public information on BC screening needs appropriate balance [22]. Although HK does not provide population-based systematic BC screening, opportunistic mammography screening services are available in public and private hospital-based units and general outpatient clinics as well as in private laboratories, for a minimal user charge to potential clients. ...
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Treatment Intensity Differences After Early-Stage Breast Cancer (ESBC) Diagnosis Depending on Participation in a Screening Program
Article
  • May 2018
Background: While population mammographic screening identifies early-stage breast cancers (ESBCs; ductal carcinoma in situ [DCIS] and invasive disease stages 1-3A), commentaries suggest that harms from overdiagnosis and overtreatment may outweigh the benefits. Apparent benefits to patients with screen-detected cancers may be due to selection bias from exclusion of interval cancers (ICs). Treatment intensity is rarely discussed, with an assumption that all ESBCs are treated similarly. We hypothesized that women diagnosed while in a screening program would receive less-intense treatment than those never or not recently screened (NRS). Methods: This was a retrospective analysis of all women aged 50-69 years managed for ESBC (invasive or DCIS) during the period 2007-2013 within a single service, comparing treatment according to screening status. Data on demographics, detection, pathology, and treatment were derived from hospital, cancer registry, and screening service records. Results: Overall, 622 patients were active screeners (AS) at diagnosis (569 screen-detected and 53 ICs) and 169 patients were NRS. AS cancers were smaller (17 mm vs. 26 mm, p < 0.0001), less likely to involve nodes (26% vs. 48%, p < 0.0001), and lower grade. For invasive cancer, NRS patients were more likely to be recommended for mastectomies [35% vs. 16%; risk ratio(RR) 2.2, p < 0.0001], axillary dissection (43% vs. 19%; RR 2.3, p < 0.0001), adjuvant chemotherapy (65% vs. 37%; RR 1.7, p < 0.0001), and postmastectomy radiotherapy (58% vs. 39%; RR 1.5, p = 0.04). Conclusion: Participants in population screening diagnosed with ESBC receive substantially less-intense treatment than non-participants. Differences persist when potential overdiagnosis is taken into account; these differences should be factored into debates around mammographic screening.
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Benefits and Harms of Breast Screening: Focused on Updated Korean Guideline for Breast Cancer Screening
Article
Full-text available
  • Mar 2016
Breast cancer is the second most common malignancy among Korean women. The incidence of breast cancer has increased since 1999, which is when the national screening program involving mammography started. Until now, the benefits of screening mammography have been emphasized, but information about its benefits and harms should be provided in a comprehensive fashion, in order to guide people toward making informed decisions. Although the main benefit of screening is reduction of breast cancer mortality, harms such as overdiagnosis, overtreatment, false positive and false negative diagnoses, and radiation-induced breast cancer, can all occur as a result of screening. The 2015 Korean guideline for breast cancer screening recommends biennial screening mammography for asymptomatic women aged 40 to 69 years. This review discusses the benefits and harms of screening mammography in light of evidence-based approaches obtained from randomized trials, meta-analysis, and guidelines.
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Early Detection of Cancer: Past, Present, and Future
Article
  • May 2015
Screening in both healthy and high-risk populations offers the opportunity to detect cancer early and with an increased opportunity for treatment and curative intent. Currently, a defined role for screening exists in some cancer types, but each screening test has limitations, and improved screening methods are urgently needed. Unfortunately, many cancers still lack effective screening recommendations, or in some cases, the benefits from screening are marginal when weighed against the potential for harm. Here we review the current status of cancer screening: we examine the role of traditional tumor biomarkers, describe recommended imaging for early tumor surveillance, and explore the potential of promising novel cancer markers such as circulating tumor cells (CTC) and circulating tumor DNA. Consistent challenges for all of these screening tests include limited sensitivity and specificity. The risk for overdiagnosis remains a particular concern in screening, whereby lesions of no clinical consequence may be detected and thus create difficult management decisions for the clinician and patient. If treatment is pursued following overdiagnosis, patients may be exposed to morbidity from a treatment that may not provide any true benefit. The cost-effectiveness of screening tests also needs to be an ongoing focus. The improvement of genomic and surveillance technologies, which leads to more precise imaging and the ability to characterize blood-based tumor markers of greater specificity, offers opportunities for major progress in cancer screening.
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Weedon-Fekjaer H, Romundstad PR, Vatten LJModern mammography screening and breast cancer mortality: population study. BMJ 348: g3701
Article
Full-text available
  • Jun 2014
Objective To evaluate the effectiveness of contemporary mammography screening using individual information about screening history and breast cancer mortality from public screening programmes. Design Prospective cohort study of Norwegian women who were followed between 1986 and 2009. Within that period (1995-2005), a national mammography screening programme was gradually implemented, with biennial invitations sent to women aged 50-69 years. Participants All Norwegian women aged 50-79 between 1986 and 2009. Main outcome measures Multiple Poisson regression analysis was used to estimate breast cancer mortality rate ratios comparing women who were invited to screening (intention to screen) with women who were not invited, with a clear distinction between cases of breast cancer diagnosed before (without potential for screening effect) and after (with potential for screening effect) the first invitation for screening. We took competing causes of death into account by censoring women from further follow-up who died from other causes. Based on the observed mortality reduction combined with the all cause and breast cancer specific mortality in Norway in 2009, we used the CISNET (Cancer Intervention and Surveillance Modeling Network) Stanford simulation model to estimate how many women would need to be invited to biennial mammography screening in the age group 50-69 years to prevent one breast cancer death during their lifetime. Results During 15 193 034 person years of observation (1986-2009), deaths from breast cancer occurred in 1175 women with a diagnosis after being invited to screening and 8996 women who had not been invited before diagnosis. After adjustment for age, birth cohort, county of residence, and national trends in deaths from breast cancer, the mortality rate ratio associated with being invited to mammography screening was 0.72 (95% confidence interval 0.64 to 0.79). To prevent one death from breast cancer, 368 (95% confidence interval 266 to 508) women would need to be invited to screening. Conclusion Invitation to modern mammography screening may reduce deaths from breast cancer by about 28%.
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Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SATwenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ 348: g366
Article
Full-text available
To compare breast cancer incidence and mortality up to 25 years in women aged 40-59 who did or did not undergo mammography screening. Follow-up of randomised screening trial by centre coordinators, the study's central office, and linkage to cancer registries and vital statistics databases. 15 screening centres in six Canadian provinces,1980-85 (Nova Scotia, Quebec, Ontario, Manitoba, Alberta, and British Columbia). 89 835 women, aged 40-59, randomly assigned to mammography (five annual mammography screens) or control (no mammography). Women aged 40-49 in the mammography arm and all women aged 50-59 in both arms received annual physical breast examinations. Women aged 40-49 in the control arm received a single examination followed by usual care in the community. Deaths from breast cancer. During the five year screening period, 666 invasive breast cancers were diagnosed in the mammography arm (n=44 925 participants) and 524 in the controls (n=44 910), and of these, 180 women in the mammography arm and 171 women in the control arm died of breast cancer during the 25 year follow-up period. The overall hazard ratio for death from breast cancer diagnosed during the screening period associated with mammography was 1.05 (95% confidence interval 0.85 to 1.30). The findings for women aged 40-49 and 50-59 were almost identical. During the entire study period, 3250 women in the mammography arm and 3133 in the control arm had a diagnosis of breast cancer, and 500 and 505, respectively, died of breast cancer. Thus the cumulative mortality from breast cancer was similar between women in the mammography arm and in the control arm (hazard ratio 0.99, 95% confidence interval 0.88 to 1.12). After 15 years of follow-up a residual excess of 106 cancers was observed in the mammography arm, attributable to over-diagnosis. Annual mammography in women aged 40-59 does not reduce mortality from breast cancer beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available. Overall, 22% (106/484) of screen detected invasive breast cancers were over-diagnosed, representing one over-diagnosed breast cancer for every 424 women who received mammography screening in the trial.
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Breast cancer mortality in participants of the Norwegian Breast Cancer Screening Program
Article
Full-text available
BACKGROUND The Norwegian Breast Cancer Screening Program started in 1996. To the authors' knowledge, this is the first report using individual-based data on invitation and participation to analyze breast cancer mortality among screened and nonscreened women in the program. Methods Information on dates of invitation, attendance, breast cancer diagnosis, emigration, death, and cause of death was linked by using unique 11-digit personal identification numbers assigned all inhabitants of Norway at birth or immigration. In total, 699,628 women ages 50 to 69 years without prior a diagnosis of breast cancer were invited to the program from 1996 to 2009 and were followed for breast cancer through 2009 and death through 2010. Incidence-based breast cancer mortality rate ratios (MRRs) were compared between the screened and nonscreened cohorts using a Poisson regression model. The MRRs were adjusted for calendar period, attained age, years since inclusion in the cohorts, and self-selection bias. RESULTS The crude breast cancer mortality rate was 20.7 per 100,000 women-years for the screened cohort compared with 39.7 per 100,000 women-years for the nonscreened cohort, resulting in an MRR of 0.52 (95% confidence interval, 0.47-0.59). The mortality reduction associated with attendance in the program was 43% (MRR, 0.57; 95% confidence interval, 0.51-0.64) after adjusting for calendar period, attained age, years after inclusion in the cohort, and self-selection bias. CONCLUSIONS After 15 years of follow-up, a 43% reduction in mortality was observed among women who attended the national mammographic screening program in Norway.
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Twenty-Five–Year Follow-up for Breast Cancer Incidence and Mortality of the Canadian National Breast Screening Study
Article
The Canadian National Breast Screening Study was a randomized controlled trial that compared breast cancer incidence and mortality rates between screening mammography and physical breast examination in 89,835 women, aged 40 to 59 years. The study was initiated in 1980. The results of follow-up at 11 to 16 years were previously published. The present study compared the incidence of breast cancer and mortality up to 25 years in women aged 40 to 59 years who did or did not undergo mammography screening. Follow-up data for a mean of 22 years were obtained by center coordinators, the study’s central office, and record linkage to cancer registries and vital statistics databases. The study was conducted at 15 screening centers in six Canadian provinces, (Nova Scotia, Quebec, Ontario, Manitoba, Alberta, and British Columbia). Women aged 40 to 59 years were randomly assigned to a mammography group (1 screening every year for 5 years or control group [no mammography]). Women aged 40 to 49 years in the mammography group and all women aged 50 to 59 years in both groups received annual physical breast examinations. Women aged 40 to 49 years in the control group had a single examination followed by routine care. The primary study outcome measure was death from breast cancer. During the 5-year screening period, breast tumors were detected in 1190 women (666 in the mammography group [n = 44,925] and 524 in the control group [n = 44,910]); of these women, 180 in the mammography group and 171 in the control group died of breast cancer during the 25-year follow-up period. The 25-year cumulative mortality from breast cancers diagnosed during the screening period was similar in both groups (hazard ratio, 1.05; 95% confidence interval, 0.85–1.30; P = 0.63). There was no difference in the 25-year cumulative mortality between the women aged 40 to 49 and 50 to 59 years. During the entire 25-year study period, 3250 women in the mammography group and 3133 in the control group were diagnosed with breast cancer; of these, 500 in the mammography group and 505 in the control group died of breast cancer. Thus, the cumulative mortality rates were similar in both groups; the hazard ratio was 0.99, with a 95% confidence interval of 0.88 to 1.12, P < 0.87. During the 5-year screening period, an excess of 142 cancers were observed in the mammography group, with 106 excess cancers recorded after 15 years of follow-up. This indicates that 22% (106/484) of the cancers were overdiagnosed, representing 1 overdiagnosed breast cancer for every 424 women screened with mammography. It was concluded that annual mammography screening in women aged 40 to 59 years fails to reduce breast cancer–specific mortality compared with physical examination alone or routine care.
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Benefits and Harms of Breast Cancer Screening: A Systematic Review
Article
Importance Patients need to consider both benefits and harms of breast cancer screening.Objective To systematically synthesize available evidence on the association of mammographic screening and clinical breast examination (CBE) at different ages and intervals with breast cancer mortality, overdiagnosis, false-positive biopsy findings, life expectancy, and quality-adjusted life expectancy.Evidence Review We searched PubMed (to March 6, 2014), CINAHL (to September 10, 2013), and PsycINFO (to September 10, 2013) for systematic reviews, randomized clinical trials (RCTs) (with no limit to publication date), and observational and modeling studies published after January 1, 2000, as well as systematic reviews of all study designs. Included studies (7 reviews, 10 RCTs, 72 observational, 1 modeling) provided evidence on the association between screening with mammography, CBE, or both and prespecified critical outcomes among women at average risk of breast cancer (no known genetic susceptibility, family history, previous breast neoplasia, or chest irradiation). We used summary estimates from existing reviews, supplemented by qualitative synthesis of studies not included in those reviews.Findings Across all ages of women at average risk, pooled estimates of association between mammography screening and mortality reduction after 13 years of follow-up were similar for 3 meta-analyses of clinical trials (UK Independent Panel: relative risk [RR], 0.80 [95% CI, 0.73-0.89]; Canadian Task Force: RR, 0.82 [95% CI, 0.74-0.94]; Cochrane: RR, 0.81 [95% CI, 0.74-0.87]); were greater in a meta-analysis of cohort studies (RR, 0.75 [95% CI, 0.69 to 0.81]); and were comparable in a modeling study (CISNET; median RR equivalent among 7 models, 0.85 [range, 0.77-0.93]). Uncertainty remains about the magnitude of associated mortality reduction in the entire US population, among women 40 to 49 years, and with annual screening compared with biennial screening. There is uncertainty about the magnitude of overdiagnosis associated with different screening strategies, attributable in part to lack of consensus on methods of estimation and the importance of ductal carcinoma in situ in overdiagnosis. For women with a first mammography screening at age 40 years, estimated 10-year cumulative risk of a false-positive biopsy result was higher (7.0% [95% CI, 6.1%-7.8%]) for annual compared with biennial (4.8% [95% CI, 4.4%-5.2%]) screening. Although 10-year probabilities of false-positive biopsy results were similar for women beginning screening at age 50 years, indirect estimates of lifetime probability of false-positive results were lower. Evidence for the relationship between screening and life expectancy and quality-adjusted life expectancy was low in quality. There was no direct evidence for any additional mortality benefit associated with the addition of CBE to mammography, but observational evidence from the United States and Canada suggested an increase in false-positive findings compared with mammography alone, with both studies finding an estimated 55 additional false-positive findings per extra breast cancer detected with the addition of CBE.Conclusions and Relevance For women of all ages at average risk, screening was associated with a reduction in breast cancer mortality of approximately 20%, although there was uncertainty about quantitative estimates of outcomes for different breast cancer screening strategies in the United States. These findings and the related uncertainty should be considered when making recommendations based on judgments about the balance of benefits and harms of breast cancer screening.
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Abolishing Mammography Screening Programs? A View From the Swiss Medical Board
Article
In January 2013, the Swiss Medical Board, an independent health technology assessment initiative under the auspices of the Conference of Health Ministers of the Swiss Cantons, the Swiss Medical Association, and the Swiss Academy of Medical Sciences, was mandated to prepare a review of mammography screening. The two of us, a medical ethicist and a clinical epidemiologist, were members of the expert panel that appraised the evidence and its implications. The other members were a clinical pharmacologist, an oncologic surgeon, a nurse scientist, a lawyer, and a health economist. As we embarked on the project, we were aware of the . . .
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Comparative analysis of breast cancer mortality following mammography screening in Denmark and Norway
Article
Background Denmark and Norway are the best countries to study effects of mammography screening, because they are the only countries with stepwise introduction of nationwide mammography screening, enabling comparative effectiveness studies of high quality. Although Denmark and Norway are countries with similar populations and health care systems, reported reductions in breast cancer mortality (incidence-based) caused by screening differed vastly; 25% in Denmark versus 10% in Norway. This study explores reasons for this difference.
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"Citizens' jury" disagrees over whether screening leaflet should put reassurance before accuracy
Article
A “citizens’ jury” of 25 women, assembled this week to provide advice for the drafting of a new leaflet on breast cancer screening, has reached consensus on some of the tricky issues. The leaflet is being rewritten after criticism that it conveyed a falsely optimistic message and in the light of the Marmot review of breast cancer screening, which found that women invited to mammographic screening were three times as likely to be “overdiagnosed” as they were to have their lives saved.1 The jury did not draft a new leaflet or the covering invitation letter that will accompany it but did consider some of the central issues to be considered by those who will draft them. For example, the jury preferred the term “overtreatment” to “overdiagnosis” by a majority of 21 to four, on the grounds that it was easier to understand, and also preferred expressing benefits in terms of lives saved rather than deaths avoided, though by a smaller majority. One juror said that lives saved set a more upbeat message than deaths avoided. Put to the vote, 13 women favoured lives saved and three preferred …
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Women "jurors" are asked how to present risk-benefit ratio of breast cancer screening
Article
A “citizens’ jury” of 21 women is meeting in London this week to help draft new leaflets that will be provided to women in England who are invited to attend breast cancer screening. The jury, made up of women of screening age recruited on the streets of London, will help draft a form of words for the leaflets and invitation letters that reflect the findings of the Marmot review of breast cancer screening, which reported last month.1 The existing leaflets have been criticised as failing to strike the right balance between the risks and benefits of screening. The review, chaired by Michael Marmot, director of University College London’s Institute for Health Equity, found that for every life saved by mammographic screening, three women …
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