Health benefits and harms of mammography screening in older women (75+ years)-a systematic review.

BACKGROUND: There is little evidence on the balance between potential benefits and harms of mammography screening in women 75 years and older. The aim of this systematic review was to synthesise the evidence on the outcomes of mammography screening in women aged 75 years and older. METHODS: A systematic review of mammography screening studies in women aged 75 years and over. RESULTS: Thirty-six studies were included in this review: 27 observational studies and 9 modelling studies. Many of the included studies used no or uninformative comparison groups resulting in a potential bias towards the benefits of screening. Despite this, there was mixed evidence about the benefits and harms of continuing mammography screening beyond the age of 75 years. Some studies showed a beneficial effect on breast cancer mortality, and other studies showed no effect on mortality. Some studies showed some harms (false positive tests and recalls) being comparable to those in younger age-groups, with other studies showing increase in false positive screens and biopsies in older age-group. Although reported in fewer studies, there was consistent evidence of increased overdiagnosis in older age-groups. CONCLUSION: There is limited evidence available to make a recommendation for/against continuing breast screening beyond the age of 75 years. Future studies should use more informative comparisons and should estimate overdiagnosis given potentially substantial harm in this age-group due to competing causes of death. This review was prospectively registered with PROSPERO (CRD42020203131).

Frequency and characteristics of errors by artificial intelligence (AI) in reading screening mammography: a systematic review.

PURPOSE: Artificial intelligence (AI) for reading breast screening mammograms could potentially replace (some) human-reading and improve screening effectiveness. This systematic review aims to identify and quantify the types of AI errors to better understand the consequences of implementing this technology. METHODS: Electronic databases were searched for external validation studies of the accuracy of AI algorithms in real-world screening mammograms. Descriptive synthesis was performed on error types and frequency. False negative proportions (FNP) and false positive proportions (FPP) were pooled within AI positivity thresholds using random-effects meta-analysis. RESULTS: Seven retrospective studies (447,676 examinations; published 2019-2022) met inclusion criteria. Five studies reported AI error as false negatives or false positives. Pooled FPP decreased incrementally with increasing positivity threshold (71.83% [95% CI 69.67, 73.90] at Transpara 3 to 10.77% [95% CI 8.34, 13.79] at Transpara 9). Pooled FNP increased incrementally from 0.02% [95% CI 0.01, 0.03] (Transpara 3) to 0.12% [95% CI 0.06, 0.26] (Transpara 9), consistent with a trade-off with FPP. Heterogeneity within thresholds reflected algorithm version and completeness of the reference standard. Other forms of AI error were reported rarely (location error and technical error in one study each). CONCLUSION: AI errors are largely interpreted in the framework of test accuracy. FP and FN errors show expected variability not only by positivity threshold, but also by algorithm version and study quality. Reporting of other forms of AI errors is sparse, despite their potential implications for adoption of the technology. Considering broader types of AI error would add nuance to reporting that can inform inferences about AI's utility.

Randomized Trial of Information for Older Women About Cessation of Breast Cancer Screening Invitations.

BACKGROUND: Older women receive no information about why Australia's breast screening program (BreastScreen) invitations cease after 74 years. We tested how providing older women with the rationale for breast screening cessation impacted informed choice (adequate knowledge; screening attitudes aligned with intention). METHODS: In a three-arm online randomized trial, eligible participants were females aged 70-74 years who had recently participated in breast screening (within 5 years), without personal breast cancer history, recruited through Qualtrics. Participants read a hypothetical scenario in which they received a BreastScreen letter reporting no abnormalities on their mammogram. They were randomized to receive the letter: (1) without any rationale for screening cessation (control); (2) with screening cessation rationale in printed-text form (e.g., downsides of screening outweigh the benefits after age 74); or (3) with screening cessation rationale presented in an animation video form. The primary outcome was informed choice about continuing/stopping breast screening beyond 74 years. RESULTS: A total of 376 participant responses were analyzed. Compared to controls (n = 122), intervention arm participants (text [n = 132] or animation [n = 122]) were more likely to make an informed choice (control 18.0%; text 32.6%, p = .010; animation 40.5%, p < .001). Intervention arm participants had more adequate knowledge (control 23.8%; text 59.8%, p < .001; animation 68.9%, p < .001), lower screening intentions (control 17.2%; text 36.4%, p < .001; animation 49.2%, p < .001), and fewer positive screening attitudes regarding screening for themselves in the animation arm, but not in the text arm (control 65.6%; text 51.5%, p = .023; animation 40.2%, p < .001). CONCLUSIONS: Providing information to older women about the rationale for breast cancer screening cessation increased informed decision-making in a hypothetical scenario. This study is an important first step in improving messaging provided by national cancer screening providers direct to older adults. Further research is needed to assess the impact of different elements of the intervention and the impact of providing this information in clinical practice, with more diverse samples. TRIAL REGISTRATION: ANZCTRN12623000033640.

Lung cancer screening program factors that influence psychosocial outcomes: A systematic review.

OBJECTIVES: Lung cancer screening (LCS) programs are being designed and implemented globally. Early data suggests that the psychosocial impacts of LCS are influenced by program factors, but evidence synthesis is needed. This systematic review aimed to elucidate the impact of service-level factors on psychosocial outcomes to inform optimal LCS program design and future implementation. METHODS: Four databases were searched from inception to July 2023. Inclusion criteria were full-text articles published in English that reported an association between any program factors and psychosocial outcomes experienced during LCS. Study quality was appraised, and findings were synthesised narratively. RESULTS: Thirty-two articles were included; 29 studies were assessed at high or moderate risk of bias. Study designs were RCT (n = 3), pre-post (n = 6), cross-sectional (n = 12), mixed-methods (n = 1), and qualitative (n = 10) studies, and conducted primarily in the USA (n = 25). Findings suggested that targeted interventions can improve smoking-related or decisional psychosocial outcomes (e.g., smoking cessation interventions increase readiness/motivation to quit) but impacts of interventions on other psychological outcomes were varied. There was limited evidence reporting association between service delivery components and psychological outcomes, and results suggested moderation by individual aspects (e.g., expectation of results, baseline anxiety). Opportunities for discussion were key in reducing psychological harm. CONCLUSIONS: Certain program factors are reportedly associated with psychosocial impacts of LCS, but study heterogeneity and quality necessitate more real-world studies. Future work should examine (a) implementation of targeted interventions and high-value discussion during LCS, and (b) optimal methods and timing of risk and result communication, to improve psychosocial outcomes while reducing time burden for clinicians.

Screening and diagnostic breast MRI: how do they impact surgical treatment? Insights from the MIPA study.

OBJECTIVES: To report mastectomy and reoperation rates in women who had breast MRI for screening (S-MRI subgroup) or diagnostic (D-MRI subgroup) purposes, using multivariable analysis for investigating the role of MRI referral/nonreferral and other covariates in driving surgical outcomes. METHODS: The MIPA observational study enrolled women aged 18-80 years with newly diagnosed breast cancer destined to have surgery as the primary treatment, in 27 centres worldwide. Mastectomy and reoperation rates were compared using non-parametric tests and multivariable analysis. RESULTS: A total of 5828 patients entered analysis, 2763 (47.4%) did not undergo MRI (noMRI subgroup) and 3065 underwent MRI (52.6%); of the latter, 2441/3065 (79.7%) underwent MRI with preoperative intent (P-MRI subgroup), 510/3065 (16.6%) D-MRI, and 114/3065 S-MRI (3.7%). The reoperation rate was 10.5% for S-MRI, 8.2% for D-MRI, and 8.5% for P-MRI, while it was 11.7% for noMRI (p ≤ 0.023 for comparisons with D-MRI and P-MRI). The overall mastectomy rate (first-line mastectomy plus conversions from conserving surgery to mastectomy) was 39.5% for S-MRI, 36.2% for P-MRI, 24.1% for D-MRI, and 18.0% for noMRI. At multivariable analysis, using noMRI as reference, the odds ratios for overall mastectomy were 2.4 (p < 0.001) for S-MRI, 1.0 (p = 0.957) for D-MRI, and 1.9 (p < 0.001) for P-MRI. CONCLUSIONS: Patients from the D-MRI subgroup had the lowest overall mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). This analysis offers an insight into how the initial indication for MRI affects the subsequent surgical treatment of breast cancer. KEY POINTS: • Of 3065 breast MRI examinations, 79.7% were performed with preoperative intent (P-MRI), 16.6% were diagnostic (D-MRI), and 3.7% were screening (S-MRI) examinations. • The D-MRI subgroup had the lowest mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). • The S-MRI subgroup had the highest mastectomy rate (39.5%) which aligns with higher-than-average risk in this subgroup, with a reoperation rate (10.5%) not significantly different to that of all other subgroups.

Preoperative breast MRI positively impacts surgical outcomes of needle biopsy-diagnosed pure DCIS: a patient-matched analysis from the MIPA study.

OBJECTIVES: To investigate the influence of preoperative breast MRI on mastectomy and reoperation rates in patients with pure ductal carcinoma in situ (DCIS). METHODS: The MIPA observational study database (7245 patients) was searched for patients aged 18-80 years with pure unilateral DCIS diagnosed at core needle or vacuum-assisted biopsy (CNB/VAB) and planned for primary surgery. Patients who underwent preoperative MRI (MRI group) were matched (1:1) to those who did not receive MRI (noMRI group) according to 8 confounding covariates that drive referral to MRI (age; hormonal status; familial risk; posterior-to-nipple diameter; BI-RADS category; lesion diameter; lesion presentation; surgical planning at conventional imaging). Surgical outcomes were compared between the matched groups with nonparametric statistics after calculating odds ratios (ORs). RESULTS: Of 1005 women with pure unilateral DCIS at CNB/VAB (507 MRI group, 498 noMRI group), 309 remained in each group after matching. First-line mastectomy rate in the MRI group was 20.1% (62/309 patients, OR 2.03) compared to 11.0% in the noMRI group (34/309 patients, p = 0.003). The reoperation rate was 10.0% in the MRI group (31/309, OR for reoperation 0.40) and 22.0% in the noMRI group (68/309, p < 0.001), with a 2.53 OR of avoiding reoperation in the MRI group. The overall mastectomy rate was 23.3% in the MRI group (72/309, OR 1.40) and 17.8% in the noMRI group (55/309, p = 0.111). CONCLUSIONS: Compared to those going directly to surgery, patients with pure DCIS at CNB/VAB who underwent preoperative MRI had a higher OR for first-line mastectomy but a substantially lower OR for reoperation. CLINICAL RELEVANCE STATEMENT: When confounding factors behind MRI referral are accounted for in the comparison of patients with CNB/VAB-diagnosed pure unilateral DCIS, preoperative MRI yields a reduction of reoperations that is more than twice as high as the increase in overall mastectomies. KEY POINTS: • Confounding factors cause imbalance when investigating the influence of preoperative MRI on surgical outcomes of pure DCIS. • When patient matching is applied to women with pure unilateral DCIS, reoperation rates are significantly reduced in women who underwent preoperative MRI. • The reduction of reoperations brought about by preoperative MRI is more than double the increase in overall mastectomies.

Psychosocial outcomes and health service use after notifying women participating in population breast screening when they have dense breasts: a BreastScreen Queensland randomised controlled trial.

BACKGROUND: Robust evidence regarding the benefits and harms of notifying Australian women when routine breast screening identifies that they have dense breasts is needed for informing future mammography population screening practice and policy. OBJECTIVES: To assess the psychosocial and health services use effects of notifying women participating in population-based breast cancer screening that they have dense breasts; to examine whether the mode of communicating this information about its implications (print, online formats) influences these effects. METHODS AND ANALYSIS: The study population comprises women aged 40 years or older who attend BreastScreen Queensland Sunshine Coast services for mammographic screening and are found to have dense breasts (BI-RADS density C or D). The randomised controlled trial includes three arms (952 women each): standard BreastScreen care (no notification of breast density; control arm); notification of dense breasts in screening results letter and print health literacy-sensitive information (intervention arm 1) or a link or QR code to online video-based health literacy-sensitive information (intervention arm 2). Baseline demographic data will be obtained from BreastScreen Queensland. Outcomes data will be collected in questionnaires at baseline and eight weeks, twelve months, and 27 months after breast screening. Primary outcomes will be psychological outcomes and health service use; secondary outcomes will be supplemental screening outcomes, cancer worry, perceived breast cancer risk, knowledge about breast density, future mammographic screening intentions, and acceptability of notification about dense breasts. ETHICS APPROVAL: Gold Coast Hospital and Health Service Ethics Committee (HREC/2023/QGC/89770); Sunshine Coast Hospital and Health Service Research Governance and Development (SSA/2023/QSC/89770). DISSEMINATION OF FINDINGS: Findings will be reported in peer-reviewed journals and at national and international conferences. They will also be reported to BreastScreen Queensland, BreastScreen Australia, Cancer Australia, and other bodies involved in cancer care and screening, including patient and support organisations. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12623000001695p (prospective: 9 January 2023).

"I haven't had that information, even though I think I'm really well-informed about most things": a qualitative focus group study on Australian women's understanding and views of potentially modifiable risk factors for breast cancer.

BACKGROUND: Building health literacy about potentially modifiable risk factors for breast cancer may help to empower women to make more informed decisions about their breast health; however there has been limited qualitative research on this topic. This study aimed to explore current knowledge, understanding and experience of potentially modifiable risk factors for breast cancer, and views on current and future communication strategies for this information and related interventions. METHODS: Qualitative study using online focus groups via Zoom in October-November 2022. A diverse sample of women from the Australian community aged 40-74 years were recruited. RESULTS: Fifty-one women from a range of socioeconomic backgrounds took part in nine focus groups. General knowledge of risk factors for breast cancer in the community is limited, particularly in relation to modifiable factors such as alcohol consumption and postmenopausal obesity, with many women describing feelings of 'shock' following this information. Women overwhelming believed that information on modifiable risk factors for breast cancer should be communicated more widely, however communication preferences for receiving this information varied. There was a strong preference amongst the women for a cascade of information which they believed may then help target greater number of women of all ages and backgrounds. Despite worry about long-term compliance, women also supported various lifestyle interventions which may help them and other women to reduce their overall risk. CONCLUSIONS: Findings from this study highlight the need for more widespread community communication and education about risk factors for breast, in particular potentially modifiable risk factors such as alcohol consumption and postmenopausal obesity. As breast screening programs in Australia and globally begin to evaluate the potential for risk-related screening this will provide an additional context for primary prevention, hence planning of messaging and piloting of lifestyle-related prevention strategies in breast cancer is needed now. Gaining an understanding of women's preferences for communication and forms of interventions is vital to ensure their engagement.

Practical, epistemic and normative implications of algorithmic bias in healthcare artificial intelligence: a qualitative study of multidisciplinary expert perspectives.

BACKGROUND: There is a growing concern about artificial intelligence (AI) applications in healthcare that can disadvantage already under-represented and marginalised groups (eg, based on gender or race). OBJECTIVES: Our objectives are to canvas the range of strategies stakeholders endorse in attempting to mitigate algorithmic bias, and to consider the ethical question of responsibility for algorithmic bias. METHODOLOGY: The study involves in-depth, semistructured interviews with healthcare workers, screening programme managers, consumer health representatives, regulators, data scientists and developers. RESULTS: Findings reveal considerable divergent views on three key issues. First, views on whether bias is a problem in healthcare AI varied, with most participants agreeing bias is a problem (which we call the bias-critical view), a small number believing the opposite (the bias-denial view), and some arguing that the benefits of AI outweigh any harms or wrongs arising from the bias problem (the bias-apologist view). Second, there was a disagreement on the strategies to mitigate bias, and who is responsible for such strategies. Finally, there were divergent views on whether to include or exclude sociocultural identifiers (eg, race, ethnicity or gender-diverse identities) in the development of AI as a way to mitigate bias. CONCLUSION/SIGNIFICANCE: Based on the views of participants, we set out responses that stakeholders might pursue, including greater interdisciplinary collaboration, tailored stakeholder engagement activities, empirical studies to understand algorithmic bias and strategies to modify dominant approaches in AI development such as the use of participatory methods, and increased diversity and inclusion in research teams and research participant recruitment and selection.

Differential detection by breast density for digital breast tomosynthesis versus digital mammography population screening: a systematic review and meta-analysis.

BACKGROUND: We examined whether digital breast tomosynthesis (DBT) detects differentially in high- or low-density screens. METHODS: We searched six databases (2009-2020) for studies comparing DBT and digital mammography (DM), and reporting cancer detection rate (CDR) and/or recall rate by breast density. Meta-analysis was performed to pool incremental CDR and recall rate for DBT (versus DM) for high- and low-density (dichotomised based on BI-RADS) and within-study differences in incremental estimates between high- and low-density. Screening settings (European/US) were compared. RESULTS: Pooled within-study difference in incremental CDR for high- versus low-density was 1.0/1000 screens (95% CI: 0.3, 1.6; p = 0.003). Estimates were not significantly different in US (0.6/1000; 95% CI: 0.0, 1.3; p = 0.05) and European (1.9/1000; 95% CI: 0.3, 3.5; p = 0.02) settings (p for subgroup difference = 0.15). For incremental recall rate, within-study differences between density subgroups differed by setting (p < 0.001). Pooled incremental recall was less in high- versus low-density screens (-0.9%; 95% CI: -1.4%, -0.4%; p < 0.001) in US screening, and greater (0.8%; 95% CI: 0.3%, 1.3%; p = 0.001) in European screening. CONCLUSIONS: DBT has differential incremental cancer detection and recall by breast density. Although incremental CDR is greater in high-density, a substantial proportion of additional cancers is likely to be detected in low-density screens. Our findings may assist screening programmes considering DBT for density-tailored screening.

Magnetic resonance imaging before breast cancer surgery: results of an observational multicenter international prospective analysis (MIPA).

OBJECTIVES: Preoperative breast magnetic resonance imaging (MRI) can inform surgical planning but might cause overtreatment by increasing the mastectomy rate. The Multicenter International Prospective Analysis (MIPA) study investigated this controversial issue. METHODS: This observational study enrolled women aged 18-80 years with biopsy-proven breast cancer, who underwent MRI in addition to conventional imaging (mammography and/or breast ultrasonography) or conventional imaging alone before surgery as routine practice at 27 centers. Exclusion criteria included planned neoadjuvant therapy, pregnancy, personal history of any cancer, and distant metastases. RESULTS: Of 5896 analyzed patients, 2763 (46.9%) had conventional imaging only (noMRI group), and 3133 (53.1%) underwent MRI that was performed for diagnosis, screening, or unknown purposes in 692/3133 women (22.1%), with preoperative intent in 2441/3133 women (77.9%, MRI group). Patients in the MRI group were younger, had denser breasts, more cancers ≥ 20 mm, and a higher rate of invasive lobular histology than patients who underwent conventional imaging alone (p < 0.001 for all comparisons). Mastectomy was planned based on conventional imaging in 22.4% (MRI group) versus 14.4% (noMRI group) (p < 0.001). The additional planned mastectomy rate in the MRI group was 11.3%. The overall performed first- plus second-line mastectomy rate was 36.3% (MRI group) versus 18.0% (noMRI group) (p < 0.001). In women receiving conserving surgery, MRI group had a significantly lower reoperation rate (8.5% versus 11.7%, p < 0.001). CONCLUSIONS: Clinicians requested breast MRI for women with a higher a priori probability of receiving mastectomy. MRI was associated with 11.3% more mastectomies, and with 3.2% fewer reoperations in the breast conservation subgroup. KEY POINTS: • In 19% of patients of the MIPA study, breast MRI was performed for screening or diagnostic purposes. • The current patient selection to preoperative breast MRI implies an 11% increase in mastectomies, counterbalanced by a 3% reduction of the reoperation rate. • Data from the MIPA study can support discussion in tumor boards when preoperative MRI is under consideration and should be shared with patients to achieve informed decision-making.

Long term risk of distant metastasis in women with non-metastatic breast cancer and survival after metastasis detection: a population-based linked health records study.

OBJECTIVES: To estimate the long term risk of distant metastases (DM) for women with initial diagnoses of non-metastatic breast cancer; to estimate breast cancer-specific and overall survival for women with DM. DESIGN: Population-based health record linkage study. SETTING, PARTICIPANTS: Women diagnosed with localised or regional primary breast cancer recorded in the NSW Cancer Registry, 2001-2002. MAJOR OUTCOME MEASURES: Time from breast cancer diagnosis to first DM, time from first DM to death from breast cancer. SECONDARY OUTCOME: time to death from any cause. RESULTS: 6338 women were diagnosed with non-metastatic breast cancer (localised, 3885; regional, 2453; median age, 59 years [IQR, 49-69 years]). DM were recorded (to 30 September 2016) for 1432 women (23%; median age, 62 years [IQR, 51-73 years]). The 14-year cumulative DM incidence was 22.2% (95% CI, 21.1-23.2%; localised disease: 14.3% [95% CI, 13.2-15.4%]; regional disease: 34.7% [95% CI, 32.8-36.6%]). Annual hazard of DM was highest during the second year after breast cancer diagnosis (localised disease: 2.8%; 95% CI, 2.3-3.3%; regional disease: 9.1%; 95% CI, 7.8-10.3%); from year five it was about 1% for those with localised disease, from year seven about 2% for women with regional disease at diagnosis. Five years after diagnosis, the 5-year conditional probability of DM was 4.4% (95% CI, 3.7-5.1%) for women with localised and 10.4% (95% CI, 9.1-12.0%) for those with regional disease at diagnosis. Median breast cancer-specific survival from first DM record date was 28 months (95% CI, 25-31 months); the annual hazard of breast cancer death after the first DM record declined from 36% (95% CI, 33-40%) during the first year to 14% (95% CI, 11-18%) during the fourth year since detection. CONCLUSIONS: DM risk declines with time from diagnosis of non-metastatic breast cancer, and the annual risk of dying from breast cancer declines with time from initial DM detection. These findings can be used to inform patients at follow-up about changes in risk over time since diagnosis and for planning health services.

The impact of mandatory mammographic breast density notification on supplemental screening practice in the United States: a systematic review.

PURPOSE: Dense breast tissue is an independent risk factor for breast cancer and lowers the sensitivity of screening mammography. Supplemental screening with ultrasound or MRI improves breast cancer detection rate but has potential harms. Breast density notification (BDN) legislation has been introduced in the United States (US) and its impact on supplemental screening practice is unclear. This study systematically reviewed current evidence to explore the impact of BDN on supplemental screening practice in the US. METHODS: Medline, PubMed, Embase, Cochrane and the Cinhal Library databases were searched (2009-August 2020). Studies were assessed for eligibility, data were extracted and summarised, and study quality was evaluated. RESULTS: Evidence from the included studies (n = 14) predominantly showed that BDN legislation increased the overall utilisation of supplemental screening by 0.5-143%. This effect was amplified if the notification included a follow-up telephone call informing women about additional screening benefits, and if the state's law mandated insurance cover for supplemental screening. Likelihood of supplemental screening was also influenced by history of breast biopsy and family history of breast cancer, race, age, socioeconomic status, density category, and physician's specialty and region. Some studies reported increases in biopsy rate (up to 4%) and cancer detection rate (up to 11%) after implementation of BDN legislation. CONCLUSION: BDN leads to increased use of supplemental screening. This has implications for women and the health system. These findings can help inform current and future screening programs, where breast density notification is currently implemented or being considered.

Interval and Subsequent Round Breast Cancer in a Randomized Controlled Trial Comparing Digital Breast Tomosynthesis and Digital Mammography Screening.

Background Prevalent digital breast tomosynthesis (DBT) has shown higher cancer detection rates and lower recall rates compared with those of digital mammography (DM). However, data are limited on rates and histopathologic tumor characteristics of interval and subsequent round screen-detected cancers for DBT. Purpose To follow women randomized to screening with DBT or DM and to investigate rates and tumor characteristics of interval and subsequent round screen-detected cancers. Materials and Methods To-Be is a randomized controlled trial comparing the outcome of DBT and DM in organized breast cancer screening. The trial included 28 749 women, with 22 306 women returning for subsequent DBT screening 2 years later (11 201 and 11 105 originally screened with DBT and DM, respectively). Differences in rates, means, and distribution of histopathologic tumor characteristics between women prevalently screened with DBT versus DM were evaluated with Z tests, t tests, and χ2 tests. Relative risk (RR) with 95% CIs was calculated for the cancer rates. Results Interval cancer rates were 1.4 per 1000 screens (20 of 14 380; 95% CI: 0.9, 2.1) for DBT versus 2.0 per 1000 screens (29 of 14 369; 95% CI: 1.4, 2.9; P = .20) for DM. The rates of subsequent round screen-detected cancer were 8.1 per 1000 (95% CI: 6.6, 10.0) for women originally screened with DBT and 9.1 per 1000 (95% CI: 7.4, 11.0; P = .43) for women screened with DM. The distribution of tumor characteristics did not differ between groups for either interval or subsequent screen-detected cancer. The RR of interval cancer was 0.69 (95% CI: 0.39, 1.22; P = .20) for DBT versus DM, whereas RR of subsequent screen-detected cancer for women prevalently screened with DBT versus DM was 0.89 (95% CI: 0.67, 1.19; P = .43). Conclusion Rates of interval or subsequent round screen-detected cancers and their tumor characteristics did not differ between women originally screened with digital breast tomosynthesis (DBT) versus digital mammography. The analysis suggests that the benefits of prevalent DBT screening did not come at the expense of worse downstream screening performance measures in a population-based screening program. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Taourel in this issue.

Digital Mammography and Breast Tomosynthesis Performance in Women with a Personal History of Breast Cancer, 2007-2016.

Background Since 2007, digital mammography and digital breast tomosynthesis (DBT) replaced screen-film mammography. Whether these technologic advances have improved diagnostic performance has, to the knowledge of the authors, not yet been established. Purpose To evaluate the performance and outcomes of surveillance mammography (digital mammography and DBT) performed from 2007 to 2016 in women with a personal history of breast cancer and compare with data from 1996 to 2007 and the performance of digital mammography screening benchmarks. Materials and Methods In this observational cohort study, five Breast Cancer Surveillance Consortium registries provided prospectively collected mammography data linked with tumor registry and pathologic outcomes. This study identified asymptomatic women with American Joint Committee on Cancer anatomic stages 0-III primary breast cancer who underwent surveillance mammography from 2007 to 2016. The primary outcome was a second breast cancer diagnosis within 1 year of mammography. Performance measures included the recall rate, cancer detection rate, interval cancer rate, positive predictive value of biopsy recommendation, sensitivity, and specificity. Results Among 32 331 women who underwent 117 971 surveillance mammographic examinations (112 269 digital mammographic examinations and 5702 DBT examinations), the mean age at initial diagnosis was 59 years ± 12 (standard deviation). Of 1418 second breast cancers diagnosed, 998 were surveillance-detected cancers and 420 were interval cancers. The recall rate was 8.8% (10 365 of 117 971; 95% CI: 8.6%, 9.0%), the cancer detection rate was 8.5 per 1000 examinations (998 of 117 971; 95% CI: 8.0, 9.0), the interval cancer rate was 3.6 per 1000 examinations (420 of 117 971; 95% CI: 3.2, 3.9), the positive predictive value of biopsy recommendation was 31.0% (998 of 3220; 95% CI: 29.4%, 32.7%), the sensitivity was 70.4% (998 of 1418; 95% CI: 67.9%, 72.7%), and the specificity was 98.1% (114 331 of 116 553; 95% CI: 98.0%, 98.2%). Compared with previously published studies, interval cancer rate was comparable with rates from 1996 to 2007 in women with a personal history of breast cancer and was higher than the published digital mammography screening benchmarks. Conclusion In transitioning from screen-film to digital mammography and digital breast tomosynthesis, surveillance mammography performance demonstrated minimal improvement over time and remained inferior to the performance of screening mammography benchmarks. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Moy and Gao in this issue.

Screening outcomes by risk factor and age: evidence from BreastScreen WA for discussions of risk-stratified population screening.

OBJECTIVES: To estimate rates of screen-detected and interval breast cancers, stratified by risk factor, to inform discussions of risk-stratified population screening. DESIGN: Retrospective population-based cohort study; analysis of routinely collected BreastScreen WA program clinical and administrative data. SETTING, PARTICIPANTS: All BreastScreen WA mammography screening episodes for women aged 40 years or more during 1 July 2007 - 30 June 2017. MAIN OUTCOME MEASURES: Cancer detection rate (CDR) and interval cancer rate (ICR), by risk factor. RESULTS: A total of 323 082 women were screened in 1 026 137 screening episodes (mean age, 58.5 years; SD, 8.6 years). The overall CDR was 68 (95% CI, 67-70) cancers per 10 000 screens, and the overall ICR was 9.7 (95% CI, 9.2-10.1) cancers per 10 000 women-years. Interactions between the effects on CDR of age group and five risk factors were statistically significant: personal history of breast cancer (P = 0.039), family history of breast cancer (P = 0.005), risk-relevant benign conditions (P = 0.012), hormone-replacement therapy (P = 0.002), and self-reported symptoms (P < 0.001). The influence of these risk factors (except personal history) increased with age. For ICR, only the interaction between age and hormone-replacement therapy was significant (P < 0.001), although weak interactions between age and family history of breast cancer or having dense breasts were noted (each P = 0.07). The influence of family history on ICR was significant only for women aged 40-49 years. CONCLUSIONS: Screening CDR and (for some risk factors) ICR were higher for women in some age groups with personal histories of breast cancer or risk-relevant benign breast conditions or first degree family history of breast cancer, women with dense breasts or self-reported breast-related symptoms, and women using hormone-replacement therapy. Our findings could inform the evaluation of risk-based screening.

The cost-effectiveness of digital breast tomosynthesis in a population breast cancer screening program.

OBJECTIVES: To evaluate at which sensitivity digital breast tomosynthesis (DBT) would become cost-effective compared to digital mammography (DM) in a population breast cancer screening program, given a constant estimate of specificity. METHODS: In a microsimulation model, the cost-effectiveness of biennial screening for women aged 50-75 was simulated for three scenarios: DBT for women with dense breasts and DM for women with fatty breasts (scenario 1), DBT for the whole population (scenario 2) or maintaining DM screening (reference). For DM, sensitivity was varied depending on breast density from 65 to 87%, and for DBT from 65 to 100%. The specificity was set at 96.5% for both DM and DBT. Direct medical costs were considered, including screening, biopsy and treatment costs. Scenarios were considered to be cost-effective if the incremental cost-effectiveness ratio (ICER) was below €20,000 per life year gain (LYG). RESULTS: For both scenarios, the ICER was more favourable at increasing DBT sensitivity. Compared with DM screening, 0.8-10.2% more LYGs were found when DBT sensitivity was at least 75% for scenario 1, and 4.7-18.7% when DBT sensitivity was at least 80% for scenario 2. At €96 per DBT, scenario 1 was cost-effective at a DBT sensitivity of at least 90%, and at least 95% for scenario 2. At €80 per DBT, these values decreased to 80% and 90%, respectively. CONCLUSION: DBT is more likely to be a cost-effective alternative to mammography in women with dense breasts. Whether DBT could be cost-effective in a general population highly depends on DBT costs. KEY POINTS: • DBT could be a cost-effective screening modality for women with dense breasts when its sensitivity is at least 90% at a maximum cost per screen of €96. • DBT has the potential to be cost-effective for screening all women when sensitivity is at least 90% at a maximum cost per screen of €80. • Whether DBT could be used as an alternative to mammography for screening all women is highly dependent on the cost of DBT per screen.

Solving the preoperative breast MRI conundrum: design and protocol of the MIPA study.

Despite its high diagnostic performance, the use of breast MRI in the preoperative setting is controversial. It has the potential for personalized surgical management in breast cancer patients, but two of three randomized controlled trials did not show results in favor of its introduction for assessing the disease extent before surgery. Meta-analyses showed a higher mastectomy rate in women undergoing preoperative MRI compared to those who do not. Nevertheless, preoperative breast MRI is increasingly used and a survey from the American Society of Breast Surgeons showed that 41% of respondents ask for it in daily practice. In this context, a large-scale observational multicenter international prospective analysis (MIPA study) was proposed under the guidance of the European Network for the Assessment of Imaging in Medicine (EuroAIM). The aims were (1) to prospectively and systematically collect data on consecutive women with a newly diagnosed breast cancer, not candidates for neoadjuvant therapy, who are offered or not offered breast MRI before surgery according to local practice; (2) to compare these two groups in terms of surgical and clinical endpoints, adjusting for covariates. The underlying hypotheses are that MRI does not cause additional mastectomies compared to conventional imaging, while reducing the reoperation rate in all or in subgroups of patients. Ninety-six centers applied to a web-based call; 36 were initially selected based on volume and quality standards; 27 were active for enrollment. On November 2018, the target of 7000 enrolled patients was reached. The MIPA study is presently at the analytic phase. Key Points • Breast MRI has a high diagnostic performance but its utility in the preoperative setting is controversial. • A large-scale observational multicenter prospective study was launched to compare women receiving with those not receiving preoperative MRI. • Twenty-seven centers enrolled more than 7000 patients. The study is presently at the analytic phase.

Two-view digital breast tomosynthesis versus digital mammography in a population-based breast cancer screening programme (To-Be): a randomised, controlled trial.

BACKGROUND: Digital breast tomosynthesis is an advancement of mammography, and has the potential to overcome limitations of standard digital mammography. This study aimed to compare first-generation digital breast tomo-synthesis including two-dimensional (2D) synthetic mammograms versus digital mammography in a population-based screening programme. METHODS: BreastScreen Norway offers all women aged 50-69 years two-view (craniocaudal and mediolateral oblique) mammographic screening every 2 years and does independent double reading with consensus. We asked all 32 976 women who attended the programme in Bergen in 2016-17, to participate in this randomised, controlled trial with a parallel group design. A study-specific software was developed to allocate women to either digital breast tomosynthesis or digital mammography using a 1:1 simple randomisation method based on participants' unique national identity numbers. The interviewing radiographer did the randomisation by entering the number into the software. Randomisation was done after consent and was therefore concealed from both the women and the radiographer at the time of consent; the algorithm was not disclosed to radiographers during the recruitment period. All data needed for analyses were complete 12 months after the recruitment period ended. The primary outcome measure was screen-detected breast cancer, stratified by screening technique (ie, digital breast tomosynthesis and digital mammography). A log-binomial regression model was used to estimate the efficacy of digital breast tomosynthesis versus digital mammography, defined as the crude risk ratios (RRs) with 95% CIs for screen-detected breast cancer for women screened during the recruitment period. A per-protocol approach was used in the analyses. This trial is registered at ClinicalTrials.gov, number NCT02835625, and is closed to accrual. FINDINGS: Between, Jan 14, 2016, and Dec 31, 2017, 44 266 women were invited to the screening programme in Bergen, and 32 976 (74·5%) attended. After excluding women with breast implants and women who did not consent to participate, 29 453 (89·3%) were eligible for electronic randomisation. 14 734 women were allocated to digital breast tomosynthesis and 14 719 to digital mammography. After randomisation, women with a previous breast cancer were excluded (digital breast tomosynthesis group n=314, digital mammography group n=316), women with metastases from melanoma (digital breast tomosynthesis group n=1), and women who informed the radiographer about breast symptoms after providing consent (digital breast tomosynthesis group n=39, digital mammography group n=34). After exclusions, information from 28 749 women were included in the analyses (digital breast tomosynthesis group n=14 380, digital mammography group n=14 369). The proportion of screen-detected breast cancer among the screened women did not differ between the two groups (95 [0·66%, 0·53-0·79] of 14 380 vs 87 [0·61%, 0·48-0·73] of 14 369; RR 1·09, 95% CI 0·82-1·46; p=0·56). INTERPRETATION: This study indicated that digital breast tomosynthesis including synthetic 2D mammograms was not significantly different from standard digital mammography as a screening tool for the detection of breast cancer in a population-based screening programme. Economic analyses and follow-up studies on interval and consecutive round screen-detected breast cancers are needed to better understand the effect of digital breast tomosynthesis in population-based breast cancer screening. FUNDING: Cancer Registry of Norway, Department of Radiology at Haukeland University Hospital, University of Oslo, and Research Council of Norway.

A randomized controlled trial of digital breast tomosynthesis versus digital mammography in population-based screening in Bergen: interim analysis of performance indicators from the To-Be trial.

OBJECTIVES: To describe a randomized controlled trial (RCT) of digital breast tomosynthesis including synthesized two-dimensional mammograms (DBT) versus digital mammography (DM) in a population-based screening program for breast cancer and to compare selected secondary screening outcomes for the two techniques. METHODS: This RCT, performed in Bergen as part of BreastScreen Norway, was approved by the Regional Committees for Medical Health Research Ethics. All screening attendees in Bergen were invited to participate, of which 89% (14,274/15,976) concented during the first year, and were randomized to DBT (n = 7155) or DM (n = 7119). Secondary screening outcomes were stratified by mammographic density and compared using two-sample t-tests, chi-square tests, ANOVA, negative binomial regression and tests of proportions (z tests). RESULTS: Mean reading time was 1 min 11 s for DBT and 41 s for DM (p < 0.01). Mean time spent at consensus was 3 min 12 s for DBT and 2 min 12 s for DM (p < 0.01), while the rate of cases discussed at consensus was 6.4% and 7.4%, respectively for DBT and DM (p = 0.03). The recall rate was 3.0% for DBT and 3.6% for DM (p = 0.03). For women with non-dense breasts, recall rate was 2.2% for DBT versus 3.4% for DM (p = 0.04). The rate did not differ for women with dense breasts (3.6% for both). Mean glandular dose per examination was 2.96 mGy for DBT and 2.95 mGy for DM (p = 0.433). CONCLUSIONS: Interim analysis of a screening RCT showed that DBT took longer to read than DM, but had significantly lower recall rate than DM. We found no differences in radiation dose between the two techniques. KEY POINTS: • In this RCT, DBT was associated with longer interpretation time than DM • Recall rates were lower for DBT than for DM • Mean glandular radiation dose did not differ between DBT and DM.