Neglected aspects of false positive findings of mammography in breast cancer screening: analysis of false positive cases from the Stockholm trial.

OBJECTIVES: To examine the implications of false positive results of mammography in terms of the time lag from screening and complete mammography to the point when women with false positive results are declared free of cancer; the extra examinations, biopsies, and check ups required; and the cost of these extra procedures. DESIGN: Review of women with false positive results from the Stockholm mammography screening trial. SETTING: Department of Oncology, South Hospital, Stockholm. SUBJECTS: 352 and 150 women with false positive results of mammography from the first and second screening rounds of the Stockholm trial. MAIN OUTCOME MEASURES: Extra examinations and investigations required and the cost of these procedures. RESULTS: The 352 women from the first screening round made 1112 visits to the physician and had 397 fine needle aspiration biopsies, 187 mammograms, and 90 surgical biopsies before being declared free of cancer. After six months 64% of the women (219/342) were declared cancer free. The 150 women in the second round made 427 visits to the physician and had 145 fine needle aspiration biopsies, 70 mammograms, and 28 surgical biopsies, and after six months 73% (107/147) were declared cancer free. The follow up costs of the false positive screening results were Kr2.54m (250,000 pounds) in the first round and Kr0.85m (84,000 pounds) in the second round. Women under 50 accounted for about 41% of these costs. CONCLUSIONS: The examinations and investigation carried out after false positive mammography --especially in women under 50--and the cost of these procedures are a neglected but substantial problem.     

A close call: the role of screening mammography in the fight against breast cancer: health and medicine for women: a multidisciplinary, evidence-based review of mid-life health concerns

A multidisciplinary panel debated the role of screening mammography in fighting breast cancer during the Health and Medicine for Women continuing medical education (CME) conference at Yale Medical School in September 2010. Different guidelines from professional societies have presented conflicting recommendations for patients regarding both the benefits of mammography and the appropriate age and frequency of screening. In addition, a recent longitudinal study argues that screening mammography may only offer a modest benefit in terms of reducing cancer mortality. In light of these considerations, the panel debated whether mammography should be an informed decision that must be discussed and individualized for each patient based on the context of risk factors such as family history, age, and genetic dispositions.     

American and European recommendations for screening mammography in younger women: a cultural divide?

The American Cancer Society advocates mammography screening for all women from age 40, whereas in Europe it is not recommended for women below the age of 50. Randomised prospective studies have failed to show a significant benefit from screening women aged under 50 and five potentially harmful effects of screening should be considered: lead time, overdiagnosis, radiation exposure, false positive results, and cost. Younger women must be properly informed about the potential for harm as well as for benefit before screening.     

Testing the Independence of Two Diagnostic Tests

Consider two diagnostic procedures having binary outcomes. If one of the tests results in a positive finding, a more definitive diagnostic procedure will be administered to establish the presence or absence of a disease. The use of both tests will improve the overall screening sensitivity when the two tests are independent, compared with employing two tests that are positively correlated. We estimate the correlation coefficient of the two tests and derive statistical methods for testing the independence of the two diagnostic procedures conditional on disease status. The statistical tests are used to investigate the independence of mammography and clinical breast exams aimed at establishing the benefit of early detection of breast cancer. The data used in the analysis are obtained from periodic screening examinations of three randomized clinical trials of breast cancer screening. Analysis of each of these trials confirms the independence of the clinical breast and mammography examinations. Based on these three large clinical trials, we conclude that a clinical breast exam considerably increases the overall sensitivity relative to screening with mammography alone and should be routinely included in early breast cancer detection programs.     

Application of Breast Ultrasound in a Mammography-Based Chinese Breast Screening Study

We evaluated the clinical significance of the combined use of mammography + ultrasound as a new breast screening strategy. The inclusion criteria were: (1) females aged >40yrs; (2) breast cancer diagnosis by the breast image screening personnel at FUSCC; (3) screening by both ultrasound and mammography; (4) mammographic/sonographic images analyzed independently by different radiologists; and (5) follow-up for at least 1 year. Fifty-four women were enrolled. The analysis included diagnostic sensitivity of mammography, ultrasound, and mammography + ultrasound. The sensitivities of mammography and mammography + ultrasound were compared overall as well as among different age groups/breast densities. The screening sensitivity of mammography, ultrasound, and mammography + ultrasound was 79.6, 57.4, and 92.6 %, respectively. The difference between mammography and mammography + ultrasound was significant (P < 0.05). The benefit of including ultrasound with mammography as a new breast image screening strategy was found statistically significant in patients with dense breast on mammogram while it was non-significant in younger (<50 years) women. We, therefore, concluded that mammography + ultrasound increased the diagnostic sensitivity of breast screening; hence it was more desirable for women with dense breast on mammography.     

Screening with mammography organized by family physicians teams: what have we learnt?

The mammography, recommended as standard method for screening on breast cancer, can reveal suspicious lesions early enough to anable cancer elimination in entirely. Experience with women of the target population, 50-69 years old, included in the mass screening programs, show the reduction in the specific mortality by 30%. One of the main problem in organizing the preventive programs is how to increase responsiveness of subjects to screening. In the study, based on the large sample of over 1000 of subjects and 20 family medicine practices, included in the investigation, we showed that it is possible, by a pro-active involvement of family physicians teams and intensive educational and motivational activities, to achieve high level of over 80% of responsiveness to mammography screening. Analysis of the reasons of nonresponsiveness can contribute to better understanding of the mental processes included in a self-decision making. This, as the final aim, can help family physicians in their efforts to overcome many hidden barriers which obstruct their patients to accept the mammography screening.     

An Estimate of the Variance of Estimators for Lead Time and Screening Benefit Time in Randomized Cancer Screening Trials

Variance estimators are derived for estimators of the average lead time and average benefit time due to screening in a randomized screening trial via influence functions. The influence functions demonstrate that these estimators are asymptotically equivalent to the mean difference, between the study and control case groups, in the appropriate survival times. For estimating benefit time, the survival time is measured since start of study; for estimating lead time, the survival time is measured since time of diagnosis. Asymptotic variances of these estimators can be calculated in a straightforward manner from the influence functions, and these variances can be estimated from actual trial data. The performance of the variance estimators is assessed via a simulated screening trial. The situation involving censored data is also discussed.     

How should we interpret noncompliance with screening mammography?

Primary care practitioners have an important role to play in recommending breast cancer screening to patients in the target age group. In this issue of CMAJ (see pages 1335 to 1343) Dr. Marie-Dominique Beaulieu and associates report the results of a program designed to maximize utilization of screening mammography. Only two thirds of eligible women for whom screening mammography was prescribed obtained a mammogram within the 2-month study period. However, when taken in context, this compliance rate is fairly encouraging. There are many possible reasons for noncompliance such as a need for more information or for repeated suggestions. Family physicians should not become disheartened in their efforts to increase the use of screening procedures and may find that collaboration with others in giving consistent messages will help to maximize screening rates within their patient population.     

Screening for breast cancer. Report from Edinburgh Breast Screening Clinic.

As part of a trial to determine the feasibility of screening for breast cancer, 3952 women aged 40--59 years were screened once or more over two years. They represented 82% of those invited by a personal letter from their GPs. Each woman underwent mammography, two clinical examinations, and, usually, thermography. Further investigations included needle aspiration of cysts, xeromammography, and biopsy. Of the 125 women who underwent biopsy, 18 proved to have cancer. Because of the high response rate and consequent large sample of normal women the biopsy and cancer detection rates were low. Clinical examination and mammography together were more effective in detecting significant lesions than either procedure alone, and knowledge of the mammographic findings enabled the examiner to detect more abnormalities. Screening was expensive: each cancer detected cost about 6000 pounds, excluding data processing, surgical, and pathological costs. The clinic has now adopted a more simplified screening regimen, which should reduce costs, but more accurate imaging techniques and ways of identifying high-risk cases are needed.     

Factors associated with annual-interval mammography for women in their 40s

Background: Evidence is mounting that annual mammography for women in their 40s may be the optimal schedule to reduce morbidity and mortality from breast cancer. Few studies have assessed predictors of repeat mammography on an annual interval among these women. Methods: We assessed mammography screening status among 596 insured Black and Non-Hispanic white women ages 43–49. Adherence was defined as having a second mammogram 10–14 months after a previous mammogram. We examined socio-demographic, medical and healthcare-related variables on receipt of annual-interval repeat mammograms. We also assessed barriers associated with screening. Results: 44.8% of the sample were adherent to annual-interval mammography. A history of self-reported abnormal mammograms, family history of breast cancer and never having smoked were associated with adherence. Saying they had not received mammography reminders and reporting barriers to mammography were associated with non-adherence. Four barrier categories were associated with women's non-adherence: lack of knowledge/not thinking mammograms are needed, cost, being too busy, and forgetting to make/keep appointments. Conclusions: Barriers we identified are similar to those found in other studies. Health professionals may need to take extra care in discussing mammography screening risk and benefits due to ambiguity about screening guidelines for women in their 40s, especially for women without family histories of breast cancer or histories of abnormal mammograms. Reminders are important in promoting mammography and should be coupled with other strategies to help women maintain adherence to regular mammography.     

Trends in breast cancer mortality in Sweden before and after implementation of mammography screening

Background

Incidence-based mortality modelling comparing the risk of breast cancer death in screened and unscreened women in nine Swedish counties has suggested a 39% risk reduction in women 40 to 69 years old after introduction of mammography screening in the 1980s and 1990s.

Objective

We evaluated changes in breast cancer mortality in the same nine Swedish counties using a model approach based on official Swedish breast cancer mortality statistics, robust to effects of over-diagnosis and treatment changes. Using mortality data from the NordCan database from 1974 until 2003, we estimated the change in breast cancer mortality before and after introduction of mammography screening in at least the 13 years that followed screening start.

Results

Breast mortality decreased by 16% (95% CI: 9 to 22%) in women 40 to 69, and by 11% (95% CI: 2 to 20%) in women 40 to 79 years of age.

Discussion

Without individual data it is impossible to completely separate the effects of improved treatment and health service organisation from that of screening, which would bias our results in favour of screening. There will also be some contamination of post-screening mortality from breast cancer diagnosed prior to screening, beyond our attempts to adjust for delayed benefit. This would bias against screening. However, our estimates from publicly available data suggest considerably lower benefits than estimates based on comparison of screened versus non-screened women.     

Screening Coverage Needed to Reduce Mortality from Prostate Cancer: A Living Systematic Review

IntroductionScreening for prostate cancer remains controversial because of conflicting results from the two major trials: The Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) screening trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC).ObjectiveMeta-analyze and meta-regress the available PSA screening trials.MethodsWe performed a living systematic review and meta-regression of the reduction in prostate cancer mortality as a function of the duration of screening provided in each trial. We searched PubMed, Web of Science, the Cochrane Registry, and references lists from previous meta-analyses to identify randomized trials of PSA screening. We followed PRISMA guidelines and qualified strength of evidence with a GRADE Profile.ResultsWe found 6 trials, but excluded one that also screened with trans-rectal ultrasound. We considered each ERSPC center as a separate trial. When pooling together all 11 trials we found no significant benefit from screening; however, the heterogeneity was 28.2% (95% CI: 0% to 65%). Heterogeneity was explained by variations in the duration of serial screening (I² 0%; 95% CI: 0% to 52%). When we analyzed the subgroup of trials that added more than 3 years of screening (range 3.2 to 3.8) we found a significant benefit for screening with risk ratio 0.78 (95% CI 0.65–0.94; I² = 0%; 95% CI: 0% to 69%) and a number needed to invite for screening of 1000. We downgraded the quality of evidence to moderate due to our retrospective identification of subgroups and limited data on control group screening.ConclusionsAdequate duration of screening reduces mortality from prostate cancer. The benefit, while small, compares favorably with screening for other cancers. Our projections are limited by the moderate quality of evidence.     

Geographic patterns of change over time in mammography: Differences between Black and White U.S. Medicare enrollees

U.S. Black women have higher breast cancer mortality compared to White women while their rate of ever having a mammogram has become equal to or slightly surpassed that of Whites. We mapped the distribution of change in screening mammography for Black and White female Medicare enrollees ages 67–69 from 2008 to 2012 by hospital referral region across the contiguous U.S., performed cluster analysis to assess spatial autocorrelation, and examined the screening differences between these groups in 2008 and 2012 respectively. Changes in screening mammography are not consistent across the U.S.: Black and White women have increased and decreased their use of mammography in different regions and Black women’s change patterns vary more widely.     

Budget Impact Analysis of Switching to Digital Mammography in a Population-Based Breast Cancer Screening Program: A Discrete Event Simulation Model

Objective

To assess the budgetary impact of switching from screen-film mammography to full-field digital mammography in a population-based breast cancer screening program.

Methods

A discrete-event simulation model was built to reproduce the breast cancer screening process (biennial mammographic screening of women aged 50 to 69 years) combined with the natural history of breast cancer. The simulation started with 100,000 women and, during a 20-year simulation horizon, new women were dynamically entered according to the aging of the Spanish population. Data on screening were obtained from Spanish breast cancer screening programs. Data on the natural history of breast cancer were based on US data adapted to our population. A budget impact analysis comparing digital with screen-film screening mammography was performed in a sample of 2,000 simulation runs. A sensitivity analysis was performed for crucial screening-related parameters. Distinct scenarios for recall and detection rates were compared.

Results

Statistically significant savings were found for overall costs, treatment costs and the costs of additional tests in the long term. The overall cost saving was 1,115,857€ (95%CI from 932,147 to 1,299,567) in the 10^th year and 2,866,124€ (95%CI from 2,492,610 to 3,239,638) in the 20^th year, representing 4.5% and 8.1% of the overall cost associated with screen-film mammography. The sensitivity analysis showed net savings in the long term.

Conclusions

Switching to digital mammography in a population-based breast cancer screening program saves long-term budget expense, in addition to providing technical advantages. Our results were consistent across distinct scenarios representing the different results obtained in European breast cancer screening programs.     

Predictors of Non-Adherence to Breast Cancer Screening among Hospitalized Women

Objective

Disparities in screening mammography use persists among low income women, even those who are insured, despite the proven mortality benefit. A recent study reported that more than a third of hospitalized women were non-adherent with breast cancer screening. The current study explores prevalence of socio-demographic and clinical variables associated with non-adherence to screening mammography recommendations among hospitalized women.

Patients and Methods

A cross sectional bedside survey was conducted to collect socio-demographic and clinical comorbidity data thought to effect breast cancer screening adherence of hospitalized women aged 50–75 years. Logistic regression models were used to assess the association between these factors and non-adherence to screening mammography.

Results

Of 250 enrolled women, 61% were of low income, and 42% reported non-adherence to screening guidelines. After adjustment for socio-demographic and clinical predictors, three variables were found to be independently associated with non-adherence to breast cancer screening: low income (OR = 3.81, 95%CI; 1.84–7.89), current or ex-smoker (OR = 2.29, 95%CI; 1.12–4.67), and history of stroke (OR = 2.83, 95%CI; 1.21–6.60). By contrast, hospitalized women with diabetes were more likely to be compliant with breast cancer screening (OR = 2.70, 95%CI 1.35–5.34).

Conclusion

Because hospitalization creates the scenario wherein patients are in close proximity to healthcare resources, at a time when they may be reflecting upon their health status, strategies could be employed to counsel, educate, and motivate these patients towards health maintenance. Capitalizing on this opportunity would involve offering screening during hospitalization for those who are overdue, particularly for those who are at higher risk of disease.     

Quantification of overdiagnosis in randomised trials of cancer screening: an overview and re-analysis of systematic reviews

The degree of overdiagnosis in common cancer screening trials is uncertain due to inadequate design of trials, varying definition and methods used to estimate overdiagnosis. Therefore, we aimed to quantify the risk of overdiagnosis for the most widely implemented cancer screening programmes and assess the implications of design limitations and biases in cancer screening trials on the estimates of overdiagnosis by conducting an overview and re-analysis of systematic reviews of cancer screening. We searched PubMed and the Cochrane Library from their inception dates to November 29, 2021. Eligible studies included systematic reviews of randomised trials comparing cancer screening interventions to no screening, which reported cancer incidence for both trial arms. We extracted data on study characteristics, cancer incidence and assessed the risk of bias using the Cochrane Collaboration’s risk of bias tool. We included 19 trials described in 30 articles for review, reporting results for the following types of screening: mammography for breast cancer, chest X-ray or low-dose CT for lung cancer, alpha-foetoprotein and ultrasound for liver cancer, digital rectal examination, prostate-specific antigen, and transrectal ultrasound for prostate cancer, and CA-125 test and/or ultrasound for ovarian cancer. No trials on screening for melanoma were eligible. Only one trial (5%) had low risk in all bias domains, leading to a post-hoc meta-analysis, excluding trials with high risk of bias in critical domains, finding the extent of overdiagnosis ranged from 17% to 38% across cancer screening programmes. We conclude that there is a significant risk of overdiagnosis in the included randomised trials on cancer screening. We found that trials were generally not designed to estimate overdiagnosis and many trials had high risk of biases that may draw the estimates of overdiagnosis towards the null. In effect, the true extent of overdiagnosis due to cancer screening is likely underestimated.     

Overweight in relation to tumour size and axillary lymph node involvement in postmenopausal breast cancer patients—Differences between women invited to vs. not invited to mammography in a randomized screening trial

Objectives: Overweight is associated with advanced stage at diagnosis in breast cancer patients. This could be explained by specific tumour characteristics or tumour promoting factors in the obese, but a diagnostic delay could also be of importance. Mammographic screening has caused a change towards diagnosis of less advanced tumours. This study investigates invitation to mammographic screening and the association between overweight and tumour size/axillary lymph node involvement at breast cancer diagnosis in postmenopausal women. Methods: In 1976 a randomized mammographic screening trial, inviting 50% of all women aged 45–69 was set up in Malmö, Sweden. The present analysis examined overweight (body mass index ≥25) as a determinant for large tumours (>20 mm) and axillary lymph node involvement in postmenopausal women. These associations were studied separately in patients diagnosed prior to the mammographic screening trial, in invited women and in non-invited subjects (controls). In all, 2478 postmenopausal women were diagnosed with invasive breast cancer in these groups between 1961 and 1991. Logistic regression analysis allowed adjustment for other potential determinants of tumours size and axillary lymph node involvement. Results: In women diagnosed before the onset of the screening trial and in women not invited to mammography in the trial (controls), overweight was positively associated with large tumour size and axillary node involvement. There was no statistically significant association between overweight and these factors in women invited to mammographic screening. Conclusion: Invitation to mammographic screening may be particularly important for overweight postmenopausal women in order to detect breast tumours early.     

Need for open access non-screening mammography in a hospital with a specialist breast clinic service.

OBJECTIVE--Assessment of open access non-screening mammography in a hospital with a breast clinic. DESIGN--Retrospective analysis of patients sent for first mammogram to our open access service by general practitioners and breast clinic in the year April 1989 to March 1990. SETTING--District general hospital serving 200,000 people before the introduction of breast screening. SUBJECTS--361 symptomatic women referred directly by general practitioners and 226 women referred by the breast clinic for first, non-screening mammograms. MAIN OUTCOME MEASURES--Radiographic reports on all patients. Final diagnosis in patients reported as having possible or probable neoplasm. RESULTS--Of the women referred directly by general practitioners one (0.2%) was reported as showing probable malignancy (later histologically confirmed) and 15 (4%) as showing possible malignancy (on follow up none had proved malignancy). Of the women referred by the breast clinic 38 (17%) were reported as showing probable malignancy (all had confirmed carcinomas) and 35 (15%) as showing possible malignancy (19 (54%) had proved malignancy). 18 of the proved malignancies were in women under 50 years old, 26 were in women over 64 years, and 14 were in women of screening age. 54 (93%) of the 58 patients with proved breast cancer and an abnormal mammogram had a discrete breast lump. CONCLUSIONS--General practitioners accurately divided women into low and high risk groups, resulting in few abnormalities being detected in patients referred directly for mammography. This suggests that an open access non-screening mammography service for general practitioners is unnecessary in an area with a specialist breast clinic. The large proportion of cancers in women outside of screening age emphasises the need for such clinics.     

Screening and self examination for breast cancer.

Breast cancer is the major form of cancer in women, with nearly 30,000 new cases and over 15,000 deaths in the United Kingdom each year. Breast screening by mammography has been shown in randomised trials to reduce mortality from breast cancer in women aged 50 and over. An NHS breast screening programme has been in operation in the United Kingdom since 1988. Its aim is to reduce mortality from breast cancer by 25% in the population of women invited to be screened. The uptake of mammography among the eligible population may be the single most important determinant if the programme is to be effective. Primary care teams have an important part to play in encouraging women to attend for screening and in providing information, advice, and reassurance at all stages of the screening process. To date, routine breast self examination has not been shown to be an effective method of screening for breast cancer and should not therefore be promoted as a primary screening procedure. There is, however, a case to be made for women to become more "breast aware."