Mammography Screening Program Research Articles

Breast cancer patients enrolled in the Swiss mammography screening program "donna" demonstrate prolonged survival.

We compared the survival rates of women with breast cancer (BC) detected within versus outside the mammography screening program (MSP) "donna". We merged data from the MSP with the data from corresponding cancer registries to categorize BC cases as within MSP (screen-detected and interval carcinomas) and outside the MSP. We analyzed the tumor stage distribution, tumor characteristics and the survival of the women. We further estimated hazard ratios using Cox-regressions to account for different characteristics between groups and corrected the survival rates for lead-time bias. We identified 1057 invasive (ICD-10: C50) and in-situ (D05) BC cases within the MSP and 1501 outside the MSP between 2010 and 2019 in the Swiss cantons of St. Gallen and Grisons. BC within the MSP had a higher share of stage I carcinoma (46.5% vs. 33.0%; p < 0.01), a smaller (mean) tumor size (19.1mm vs. 24.9mm, p < 0.01), and fewer recurrences and metastases in the follow-up period (6.7% vs. 15.6%, p < 0.01). The 10-year survival rates were 91.4% for women within and 72.1% for women outside the MSP (p < 0.05). Survival difference persisted but decreased when women within the same tumor stage were compared. Lead-time corrected hazard ratios for the MSP accounted for age, tumor size and Ki-67 proliferation index were 0.550 (95% CI 0.389, 0.778; p < 0.01) for overall survival and 0.469 (95% CI 0.294, 0.749; p < 0.01) for BC related survival. Women participating in the "donna" MSP had a significantly higher overall and BC related survival rate than women outside the program. Detection of BC at an earlier tumor stage only partially explains the observed differences.

Risk Factors and Mortality Among Women With Interval Breast Cancer vs Screen-Detected Breast Cancer

The risk factors for interval breast cancer (IBC) compared with those for screen-detected breast cancer (SBC) and their association with mortality outcomes have not yet been evaluated among Korean women. To evaluate risk factors associated with IBC and survival among Korean women with IBC compared with those with SBC. This retrospective cohort study used data from the Korean National Health Insurance Service Database. Women who participated in a national mammographic breast cancer screening program between January 1, 2009, and December 31, 2012, were included. Mortality outcomes were calculated from the date of breast cancer diagnosis to the date of death or December 31, 2020. Data were analyzed from March 1 to June 30, 2023. Breast cancer diagnosed within 6 to 24 months after a negative screening result (ie, IBC) or within 6 months after a positive screening result (ie, SBC). Risk factors and survival rates for IBC and SBC. This study included 8702 women with IBC (mean [SD] age, 53.3 [8.6] years) and 9492 women with SBC (mean [SD] age, 54.1 [9.0] years). Compared with SBC, the probability of IBC decreased as mammographic density increased. Lower body mass index, menopausal status, hormone replacement therapy (HRT) use, and lack of family history of breast cancer were associated with a higher likelihood of IBC. When stratified by detection time, younger age at breast cancer diagnosis and family history of breast cancer were associated with an increased likelihood of IBC diagnosed at 6 to 12 months but a decreased likelihood of IBC diagnosed at 12 to 24 months. Overall mortality of IBC was comparable with SBC, but total mortality and cancer-related mortality of IBC diagnosed between 6 and 12 months was higher than that of SBC. The findings of this cohort study suggest that breast density, obesity, and HRT use were associated with IBC compared with SBC. These findings also suggest that higher supplemental breast ultrasound use among Korean women, especially those with dense breasts, could be attributed to a lower incidence of IBC among women with dense breasts compared with women with SBC, due to greater detection. Finally, overall mortality of IBC was comparable with that of SBC.

Impact of Transfer Learning Using Local Data on Performance of a Deep Learning Model for Screening Mammography.

"Just Accepted" papers have undergone full peer review and have been accepted for publication in Radiology: Artificial Intelligence. This article will undergo copyediting, layout, and proof review before it is published in its final version. Please note that during production of the final copyedited article, errors may be discovered which could affect the content. Purpose To investigate the issues of generalizability and replication of deep learning (DL) models by assessing performance of a screening mammography DL system developed at New York University (NYU) on a local Australian dataset. Materials and Methods In this retrospective study, all individuals with biopsy and surgical pathology-proven lesions and age-matched controls were identified from a South Australian public mammography screening program (January 2010 to December 2016). The primary outcome was DL system performance, measured with the area under the receiver operating characteristic curve (AUC), in classifying invasive breast cancer or ductal carcinoma in situ (n = 425) from no malignancy (n = 490) or benign lesions (n = 44) in age-matched controls. The NYU system, including models without (NYU1) and with (NYU2) heatmaps, was tested in its original form, after training from scratch (without transfer learning; TL), after retraining with TL. Results The local test set comprised 959 individuals (mean age, 62.5 years [SD, 8.5]; all female). The original AUCs for the NYU1 and NYU2 models were 0.83 (95%CI = 0.82-0.84) and 0.89 (95%CI = 0.88-0.89), respectively. When applied in their original form to the local test set, the AUCs were 0.76 (95%CI = 0.73-0.79) and 0.84 (95%CI = 0.82-0.87), respectively. After local training without TL, the AUCs were 0.66 (95%CI = 0.62-0.69) and 0.86 (95%CI = 0.84-0.88). After retraining with TL, the AUCs were 0.82 (95%CI = 0.80-0.85) and 0.86 (95%CI = 0.84-0.88). Conclusion A deep learning system developed using a U.S. dataset showed reduced performance when applied 'out of the box' to an Australian dataset. Local retraining with transfer learning using available model weights improved model performance. ©RSNA, 2024.

Abstract PO4-18-09: SMALL: Open Surgery versus Minimally invasive vacuum-Assisted excision for smaLL screen-detected breast cancer – a UK phase III randomised multi-centre trial

Abstract Background: Mammographic screening programmes reduce breast cancer mortality but detect many small good-prognosis tumours which may not progress. Screen-detected cancers are currently treated with standard surgery and adjuvant therapies, with associated morbidities. There is a need to reduce overtreatment of good prognosis tumours and numerous studies are evaluating omission of radiotherapy in low-risk disease. However, there is little evidence to support surgical de-escalation, although percutaneous minimally invasive treatment approaches have been described. Vacuum-assisted excision (VAE) is in widespread use for management of lesions of uncertain malignant potential and benign lesions. SMALL (ISRCTN 12240119) is designed to determine the feasibility of using this approach to treat small invasive tumours detected within the UK NHS Breast Screening Programme. Methods: SMALL is a phase III multicentre randomised trial comparing standard surgery with VAE for screen-detected cancers. Main eligibility criteria are age ≥47 years, unifocal grade 1 tumours with maximum diameter 15mm, strongly ER/PR+ve and HER2-ve, with negative axillary staging. Patients are randomised 2:1 to VAE or surgery, with no axillary surgery in the VAE arm. Completeness of excision is assessed radiologically, and if excision is incomplete, patients undergo surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm but may be omitted following surgery. Co-primary end-points are: 1. Non-inferiority comparison of the requirement for a second procedure following excision 2. Single arm analysis of local recurrence (LR) at 5 years following VAE Recruitment of 800 patients will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure. This ensures sufficient patients for single arm analysis of LR rates, where expected LR free survival is 99% at 5 years, with an undesirable survival probability after VAE of 97%. To ensure that the trial as a whole only has 5% alpha, the significance level for each co-primary outcome is set at 2.5% with 90% power. The Data Monitoring Committee will monitor LR events to ensure these do not exceed 3% per year. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A novel feature of SMALL is the integration of a QuinteT Recruitment Intervention (QRI), which aims to optimise recruitment to the study. Recruitment challenges are identified by analysing recruiter/patient interviews and audio-recordings of trial discussions, and by review of trial screening logs, eligibility and recruitment data and study documentation. Solutions to address these are developed collaboratively, including individual/group recruiter feedback and recruitment tips documents. Results: SMALL opened in December 2019, but recruitment halted in 2020 for 5 months due to COVID-19. At 6th July 2023, 39 centres are open, with 300 patients randomised from 32 of these, with a randomisation rate of approximately 45%, and a per site recruitment rate of 0.4-0.5 patients/month. Despite the pandemic, SMALL achieved the internal pilot feasibility targets and continues to recruit to the main study, with estimated completion of recruitment in June 2025. Drawing from preliminary QRI findings and insights from patient representatives, a recruitment tips document has been circulated (on providing balanced information about treatments, encouraging recruiters to engage with patient preferences, and explaining randomisation). Individual recruiter feedback has commenced and wider feedback is being delivered across sites via recruitment training workshops. Conclusion: Despite pandemic-related challenges, SMALL has excellent recruitment to date and is expected to have a global impact on treatment of breast cancer within mammographic screening programmes. SMALL is funded by the UK NIHR HTA programme award 17/42/32 Citation Format: Stuart McIntosh, Charlotte Coles, David Dodwell, Kenneth Elder, Jessica Foster, Claire Gaunt, Amanda Kirkham, Iain Lyburn, Sangeetha Paramasivan, Jenna Morgan, Sarah Pinder, Shelley Potter, Tracy Roberts, Nisha Sharma, Hilary Stobart, Elizabeth Southgate, Sian Taylor-Phillips, Matthew Wallis, Daniel Rea. SMALL: Open Surgery versus Minimally invasive vacuum-Assisted excision for smaLL screen-detected breast cancer – a UK phase III randomised multi-centre trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-18-09.

Abstract PO4-07-09: CONTRAST-ENHANCED MAMMOGRAPHY IN LOCAL STAGING OF SCREEN-DETECTED BREAST CANCER: ADDITIONAL LESIONS AND CHANGES TO CLINICAL MANAGEMENT

Abstract Background BreastScreen Australia, a mammographic population screening program, provides assessment of suspected breast cancer to the point of diagnosis using a combination of conventional imaging and percutaneous biopsy. Comprehensive local staging, not performed at BreastScreen, determines the extent of disease and may identify additional clinically significant breast abnormalities. Local staging options include completion of bilateral mammographic work-up, ultrasound, and/or contrast-based imaging (CBI) (magnetic resonance imaging (MRI) or contrast-enhanced mammography (CEM)), with biopsy as required. We introduced CBI for local staging after diagnosis of screen-detected cancer at our academic hospital breast service in Melbourne, Australia. We report diagnostic findings for otherwise occult disease and their impact on treatment decisions in women who underwent CEM for local staging. Material and methods Women with screen-detected breast cancer who underwent CEM for local staging between November 2018 to April 2022 were identified retrospectively. The reporting breast-specialised radiologist compared BreastScreen and CEM images to identify additional enhancing abnormalities. Additional abnormalities were further investigated with preoperative percutaneous biopsy, surgical biopsy, or problem-solving CBI. Additional CEM-detected abnormalities were documented, with invasive cancer or DCIS recorded as true positive (TP) and any other findings as false positive (FP). Impact on surgical decisions was assessed. Results 204 patients underwent CEM. 62/204 (30%) patients had 76 additional abnormalities, of which 36 (47%) were TP and 40 (53%) FP. CEM identified otherwise occult malignant lesions in 30/204 (15%) patients. TPs comprised 75% invasive cancers and 25% DCIS. 83% (30/36) of malignant abnormalities were ipsilateral to the index lesion, while 17% (6/36) were contralateral. The majority of additional invasive cancers were Grade 2 (20/27, 74.1%), followed by Grade 1 (4/27, 14.8%) then Grade 3 (3/27, 11.1%). All additional invasive cancers had the same phenotype as the patient’s index cancer (ER+/HER2-), except for one abnormality which was ER+/HER2+ where the index cancer was ER+/HER2-. The FP abnormalities consisted of normal breast tissue (20/40, 50%), benign lesions (16/40, 40%) and atypical proliferative lesions (4/40, 10%). Occult malignancies were more common for patients with higher background parenchymal enhancement (20% for moderate/marked vs 4% for minimal/mild, p=0.0023), with no statistically significant differences found by breast density (BIRADS A or B = 12%, vs BIRADS C or D = 20%, p=0.23) or by age (40-49=38%, 50-59=13%, 60-69=13%, ³70=19%, p=0.88). Additional abnormalities found on CEM resulted in surgical management change in 45/204 (22%) patients, including wider resection (24/45), conversion to mastectomy (8/45), contralateral breast surgery (6/45), additional ipsilateral excision (5/45), and bracketing (2/45). Conclusions The use of CEM for local staging of screen-detected breast cancers identified otherwise occult malignancy in 15% of patients. Age and mammographic density did not identify groups at minimal risk of additional findings. Pathology of additional malignancy suggests it is clinically significant. CEM may improve local staging and direct appropriate management of screen-detected breast cancers. Citation Format: Caroline MacCallum, Kenneth Elder, Carolyn Nickson, Kelly Ruecker, Allan Park, Bruce Mann. CONTRAST-ENHANCED MAMMOGRAPHY IN LOCAL STAGING OF SCREEN-DETECTED BREAST CANCER: ADDITIONAL LESIONS AND CHANGES TO CLINICAL MANAGEMENT [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-07-09.

Abstract PO1-23-03: Management and risk of upgrade of Atypical Ductal Hyperplasia in the breast – a population-based retrospective cohort analysis

Abstract Introduction International guidelines recommend open surgery for Atypical Ductal Hyperplasia (ADH) in the breast due to risk of underestimating malignant disease. The aim here was to evaluate the management and risk for upgrade of lesions diagnosed as ADH in percutaneous breast biopsies in two Swedish institutions. Methods All women with a screen-detected or symptomatic ADH diagnosed on percutaneous biopsy between 2013-2022 at Sundsvall and Umeå University Hospitals were included. Women with lesions classified as Breast imaging-reporting and data system (BI-RADS) 5 (highly suspicious) or 6 (confirmed malignancy) were excluded. Data were retrieved from medical records and histopathology reports. Odds ratio (OR) and 95 % confidence intervals (CI) for upgrade to malignant diagnosis after surgery was calculated by logistic regression analysis. Results Altogether, 101 women were included, mean age 56.1 years (range 36-93 years). Most women were selected from the national mammography screening program due to microcalcifications. Biopsies were performed with vacuum-assisted biopsy (VAB)(60.4%) or core-needle biopsy (CNB)(39.6%). Forty-eight women (47.5%) underwent surgery. Presence of a first degree relative with breast cancer (p &amp;lt; 0.001), more extensive microcalcifications (p=0.01), biopsies with ADH bordering DCIS (p=0.01) and CNB as opposed to VAB (p=0.02) increased the likelihood of surgical excision. Among the women undergoing surgery, eleven were upgraded to Ductal Carcinoma in Situ and seven to invasive breast cancer (overall upgrade rate 37.5%). In these women, no variable correlating to risk of upgrade in the surgical specimen was identified. After median 74 months of follow-up (range 4-105 months), one out of 53 women managed conservatively (1.9%) developed subsequent ipsilateral DCIS. Conclusion The upgrade rate to carcinoma was 37.5% after surgery while the estimated 5-year risk of ipsilateral upgrade in women managed conservatively was 1.9%. Acknowledging the short median follow-up time, these results indicate that the selection for non-surgical management in a subset of women was appropriate. Summary of histopathological results after surgical excision of ADH Citation Format: Charlotta Wadsten, Gunilla Rask. Management and risk of upgrade of Atypical Ductal Hyperplasia in the breast – a population-based retrospective cohort analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-23-03.

Abstract 3449: Is AI-enhanced breast ultrasound ready for breast cancer screening in low-resource environments? A systematic review

Abstract Purpose. Screening mammography is unavailable in many low-resource areas. We ask if the state-of-the-art in artificial intelligence (AI)-enhanced breast ultrasound (BUS) is sufficiently accurate to be used for primary breast cancer screening in low-resource regions. Background. Since the 1980s, high-income countries have implemented mammographic screening programs, leading to breast cancer mortality reduction in screened women.1 Mammography is unavailable in many low-resource regions, such as the USAPI. Furthermore, travel difficulties and lack of radiologists hinder implementation. AI combined with portable BUS may address limitations of the high-income paradigm. In this systematic review, we ask if AI-enhanced BUS can detect/segment lesions (Objective 1) and classify lesions as cancerous (Objective 2). Methods. Two reviewers independently assessed articles from 1/1/2016 to 8/6/2023 from PubMed, Google Scholar, and citation searching. Studies which report on AI development and report performance on a patient-wise, held-out test set met the inclusion criteria. Studies were characterized by AI task and clinical application time. Dataset composition and performance were examined via narrative data synthesis. QUADAS-2 bias assessment was performed using criteria for each AI task. Success in (2) is defined by meeting minimum screening performance guidelines.2,3 Results. PubMed yielded 281 studies, Google Scholar yielded 225 studies, and a manual citation search yielded 41 studies. From 382 unique full texts evaluated, 52 articles met all inclusion criteria: 3 frame selection, 2 real-time detection, 2 combination, 14 segmentation-only, and 31 classification-only. Lesion segmentation-only models achieved a 90th percentile Dice similarity coefficient of 0.913 on generally small datasets. The best evidence for lesion cancer classification reported 0.976 area under the curve. All studies faced elevated bias and applicability concerns under QUADAS-2. Conclusion. Reported performance for (1) is insufficient to introduce AI-enhanced BUS for breast cancer screening. Evidence supporting AI-enhanced BUS for (2) is dependent on few studies relying on internal datasets, limiting generalizability. Geographically diverse clinical trials are needed to confirm and improve robustness of performance of AI-enhanced BUS for (1) and (2). References. 1. Marmot MG, et al. The benefits and harms of breast cancer screening: an independent review. British journal of cancer. 2013;108(11):2205-2240. 2. Lehman CD, et al. National Performance Benchmarks for Modern Screening Digital Mammography: Update from the Breast Cancer Surveillance Consortium. Radiology. 2017-04-01 2017;283(1):49-58. doi:10.1148/radiol.2016161174 3. Rosenberg RD, et al. Performance Benchmarks for Screening Mammography. Radiology. 2006-10-01 2006;241(1):55-66. doi:10.1148/radiol.2411051504 Citation Format: Arianna Bunnell, Dustin Valdez, Fredrik Strand, Yannik Glaser, Peter Sadowski, John A. Shepherd. Is AI-enhanced breast ultrasound ready for breast cancer screening in low-resource environments? A systematic review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3449.

Structured screening for sporadic breast cancer

The aim of secondary prevention of breast cancer is to detect the disease at the earliest curable stage and thus to reduce breast cancer-specific mortality. To this end, the nationwide population-based mammography screening program (MSP) was set up in Germany in 2005 in addition to an interdisciplinary prevention project for high-risk groups. Overview of the current state of the MSP, the upcoming age expansion, and potential further developments. Narrative review article with topic-guided literature and data search. Approximately 50% of the 70,500 new cases of breast cancer that occur each year are related to the age group of the MSP. 10years after introduction of the MSP, the incidence of advanced breast cancer stages and breast cancer-related mortality of the screening target group have steadily decreased by about one quarter, while no relevant trends were seen in the neighboring age groups at the population level. The MSP has effectively contributed to areduction of breast cancer mortality. With the expansion of the age groups to 45-75years, more women have access to structured, quality assured screening. With the use of advanced stratifications and diagnostics as well as artificial intelligence, the MSP could be further optimized.

Age-specific differences in tumour characteristics between screen-detected and non-screen-detected breast cancers in women aged 40-74 at diagnosis in Sweden from 2008 to 2017.

To analyze differences between screen-detected and non-screen-detected invasive breast cancers by tumour characteristics and age at diagnosis in the nationwide population-based mammography screening program in Sweden. Data were retrieved from the National Quality Register for Breast Cancer for 2008-2017. Logistic regression analysis was used to estimate the likelihood for a tumour to be screen-detected by tumour characteristics and age group at diagnosis. In total there were 51,429 invasive breast cancers in the target age group for mammography screening of 40-74 years. Likelihood of screen detection decreased with larger tumour size, lymph node metastases, higher histological grade and distant metastasis. Odds ratios (ORs) for negative oestrogen (ER) and progesterone (PgR) were 0.41 and 0.57; for positive HER2, 0.62; for Ki-67 high versus low, 0.49. Molecular sub-types had OR of 0.56, 0.40 and 0.28, respectively, for luminal B-like, HER2-positive and triple negative versus luminal A-like. Adjusting for tumour size (T), lymph node status (N), age, year and county at diagnosis slightly elevated the ORs. Statistically significant interactions between tumour characteristics and age were found (p < 0.05) except for ER and PgR. The age group 40-49 deviated most from the other age groups. Our study demonstrates that screen-detected invasive breast cancers had more favourable tumour characteristics than non-screen-detected after adjusting for age, year and county of diagnosis, and even after adjusting for T and N. The trend towards favourable tumour characteristics was less pronounced in the 40-49 age group compared to the other age groups, except for ER and PgR.

Management and risk of upgrade of atypical ductal hyperplasia in the breast: A population-based retrospective cohort study.

International guidelines recommend open surgery for atypical ductal hyperplasia (ADH) in the breast due to risk of underestimating malignant disease. Considering the ongoing randomized trials of active surveillance of low-risk ductal carcinoma in situ (DCIS), it seems reasonable to define a low-risk group of women with ADH where a conservative approach is appropriate. The aim here was to evaluate the management and risk for upgrade of lesions diagnosed as ADH in percutaneous breast biopsies in two Swedish hospitals. All women with a screen-detected or symptomatic breast lesion breast imaging-reporting and data system (BI-RADS) 2-4 and a percutaneous biopsy showing ADH between 2013 and 2022 at Sundsvall Hospital and Umeå University Hospital were included. Information regarding imaging, histopathology, clinical features, and management was retrieved from medical records. Odds ratio (OR) and 95% confidence intervals (CI) for upgrade to malignant diagnosis after surgery were calculated by logistic regression analysis. Altogether, 101 women were included with a mean age 56.1 (range 36-93) years. Most women were selected from the national mammography screening program due to microcalcifications. Biopsies were performed with vacuum-assisted biopsy (60.4%) or core-needle biopsy (39.6%). Forty-eight women (47.5%) underwent surgery, of which 11 were upgraded to DCIS, and 7 to invasive breast cancer (upgrade rate 37.5%). Among the 53 women managed conservatively (median follow-up 74 months), one woman (1.9%) developed subsequent ipsilateral DCIS. The combined upgrade rate was 18.8%. No clinical variable statistically significantly correlating to risk of upgrade was identified. The upgrade rate of 37.5% in women undergoing surgery compared to an estimated 5-year risk of ipsilateral malignancy at 1.9% in women managed conservatively indicate that non-surgical management of select women with ADH is feasible. Research should focus on defining reproducible criteria differentiating high-risk from low-risk ADH.

Isolating the effect of confounding from the observed survival benefit of screening participants — a methodological approach illustrated by data from the German mammography screening programme

BackgroundMammography screening programmes (MSP) aim to reduce breast cancer mortality by shifting diagnoses to earlier stages. However, it is difficult to evaluate the effectiveness of current MSP because analyses can only rely on observational data, comparing women who participate in screening with women who do not. These comparisons are subject to several biases: one of the most important is self-selection into the MSP, which introduces confounding and is difficult to control for. Here, we propose an approach to quantify confounding based on breast cancer survival analyses using readily available routine data sources.MethodsUsing data from the Cancer Registry of North Rhine-Westphalia, Germany, we estimate the relative contribution of confounding to the observed survival benefit of participants of the German MSP. This is accomplished by comparing non-participants, participants with screen-detected and participants with interval breast cancers for the endpoints “death from breast cancer” and “death from all causes other than breast cancer” — the latter being assumed to be unrelated to any MSP effect. By using different contrasts, we eliminate the effects of stage shift, lead and length time bias. The association of breast cancer detection mode with survival is analysed using Cox models in 68,230 women, aged 50–69 years, with breast cancer diagnosed in 2006–2014 and followed up until 2018.ResultsThe hazard of dying from breast cancer was lower in participants with screen-detected cancer than in non-participants (HR = 0.21, 95% CI: 0.20–0.22), but biased by lead and length time bias, and confounding. When comparing participants with interval cancers and non-participants, the survival advantage was considerably smaller (HR = 0.62, 95% CI: 0.58–0.66), due to the elimination of stage shift and lead time bias. Finally, considering only mortality from causes other than breast cancer in the latter comparison, length time bias was minimised, but a survival advantage was still present (HR = 0.63, 95% CI: 0.56–0.70), which we attribute to confounding.ConclusionsThis study shows that, in addition to stage shift, lead and length time bias, confounding is an essential component when comparing the survival of MSP participants and non-participants. We further show that the confounding effect can be quantified without explicit knowledge of potential confounders by using a negative control outcome.

Automated 3D Ultrasound as an Adjunct to Screening Mammography Programs in Dense Breast: Literature Review and Metanalysis.

Purpose: The purpose of this meta-analysis is to investigate the effectiveness of supplementing screening mammography with three-dimensional automated breast ultrasonography (3D ABUS) in improving breast cancer detection rates in asymptomatic women with dense breasts. Materials and Methods: We conducted a thorough review of scientific publications comparing 3D ABUS and mammography. Articles for inclusion were sourced from peer-reviewed journal databases, namely MEDLINE (PubMed) and Scopus, based on an initial screening of their titles and abstracts. To ensure a sufficient sample size for meaningful analysis, only studies evaluating a minimum of 20 patients were retained. Eligibility for evaluation was further limited to articles written in English. Additionally, selected studies were required to have participants aged 18 or above at the time of the study. We analyzed 25 studies published between 2000 and 2021, which included a total of 31,549 women with dense breasts. Among these women, 229 underwent mammography alone, while 347 underwent mammography in combination with 3D ABUS. The average age of the women was 50.86 years (±10 years standard deviation), with a range of 40-56 years. In our efforts to address and reduce bias, we applied a range of statistical analyses. These included assessing study variation through heterogeneity assessment, accounting for potential study variability using a random-effects model, exploring sources of bias via meta-regression analysis, and checking for publication bias through funnel plots and the Egger test. These methods ensured the reliability of our study findings. Results: According to the 25 studies included in this metanalysis, out of the total number of women, 27,495 were diagnosed with breast cancer. Of these, 211 were diagnosed through mammography alone, while an additional 329 women were diagnosed through the combination of full-field digital mammography (FFDSM) and 3D ABUS. This represents an increase of 51.5%. The rate of cancers detected per 1000 women screened was 23.25‱ (95% confidence interval [CI]: 21.20, 25.60; p < 0.001) with mammography alone. In contrast, the addition of 3D ABUS to mammography increased the number of tumors detected to 20.95‱ (95% confidence interval [CI]: 18.50, 23; p < 0.001) per 1000 women screened. Discussion: Even though variability in study results, lack of long-term outcomes, and selection bias may be present, this systematic review and meta-analysis confirms that supplementing mammography with 3D ABUS increases the accuracy of breast cancer detection in women with ACR3 to ACR4 breasts. Our findings suggest that the combination of mammography and 3D ABUS should be considered for screening women with dense breasts. Conclusions: Our research confirms that adding 3D automated breast ultrasound to mammography-only screening in patients with dense breasts (ACR3 and ACR4) significantly (p < 0.05) increases the cancer detection rate.

Pros and Cons of Pre Mammography Examination Technique Description on Pain in Mammography and Re-attending Screening Programme

Pros and Cons of Pre Mammography Examination Technique Description on Pain in Mammography and Re-attending Screening Programme

Differences in mammography screening attendance among non-Western immigrants in Denmark, Finland, Iceland and Norway

Several studies have shown that attendance rates are lower among non-Western immigrants than among natives. As the Nordic countries have quite similar health systems and populations but also differences in the organisation of their organised mammography screening programmes, differences in attendance rates could highlight organisational factors that might increase the attendance rates. Mammography screening is offered free of charge in Denmark and Finland, but not in Iceland and Norway. Contrarily to the other countries, Iceland do not send out pre-booked appointment.The study population included natives and non-Western immigrants aged 50–69 years, who had at least one invitation to the national mammography screening programmes in Denmark (2008–2017), Finland (2001–2017), Iceland (2001–2020) or Norway (2001–2015). Relative risks (RRs) of attendance were estimated and adjusted for age group and calendar period.The study population included 116.033 non-Western immigrants and more than 2 million natives. The attendance rates were significantly lower among non-Western immigrants than among natives, with an adjusted relative risk of 0.81/0.80 in Denmark and Finland, 0.62 in Norway, and 0.40 in Iceland. The lower attendance rates among immigrants in Norway and Iceland did not seem to be due to differences in birth country, immigration age, or educational level, but might be explained by organisational factors.Offering free-of-charge mammography screening in Norway and Iceland and/or including a pre-booked appointment in the invitation letters in Iceland might increase the attendance rate among non-Western immigrants.

Performance of artificial intelligence in 7533 consecutive prevalent screening mammograms from the BreastScreen Australia program.

To assess the performance of an artificial intelligence (AI) algorithm in the Australian mammography screening program which routinely uses two independent readers with arbitration of discordant results. A total of 7533 prevalent round mammograms from 2017 were available for analysis. The AI program classified mammograms into deciles on the basis of breast cancer (BC) risk. BC diagnoses, including invasive BC (IBC) and ductal carcinoma in situ (DCIS), included those from the prevalent round, interval cancers, and cancers identified in the subsequent screening round two years later. Performance was assessed by sensitivity, specificity, positive and negative predictive values, and the proportion of women recalled by the radiologists and identified as higher risk by AI. Radiologists identified 54 women with IBC and 13 with DCIS with a recall rate of 9.7%. In contrast, 51 of 54 of the IBCs and 12/13 cases of DCIS were within the higher AI score group (score 10), a recall equivalent of 10.6% (a difference of 0.9% (CI -0.03 to 1.89%, p= 0.06). When IBCs were identified in the 2017 round, interval cancers classified as false negatives or with minimal signs in 2017, and cancers from the 2019 round were combined, the radiologists identified 54/67 and 59/67 were in the highest risk AI category (sensitivity 80.6% and 88.06 % respectively, a difference that was not different statistically). As the performance of AI was comparable to that of expert radiologists, future AI roles in screening could include replacing one reader and supporting arbitration, reducing workload and false positive results. AI analysis of consecutive prevalent screening mammograms from the Australian BreastScreen program demonstrated the algorithm's ability to match the cancer detection of experienced radiologists, additionally identifying five interval cancers (false negatives), and the majority of the false positive recalls. • The AI program was almost as sensitive as the radiologists in terms of identifying prevalent lesions (51/54 for invasive breast cancer, 63/67 when including ductal carcinoma in situ). • If selected interval cancers and cancers identified in the subsequent screening round were included, the AI program identified more cancers than the radiologists (59/67 compared with 54/67, sensitivity 88.06 % and 80.6% respectively p = 0.24). • The high negative predictive value of a score of 1-9 would indicate a role for AI as a triage tool to reduce the recall rate (specifically false positives).

Expanding mammography screening for women aged 40–80 years: evidence from a modeling approach using real-world data

If a mammography screening program (MS) is to be expanded, the benefit must be demonstrated for each additional age cohort. For the age interval between 40 and 80 years, the association between tumor-related and tumor-independent mortality of 21 2-year cohorts is modeled using up-to-date, valid data to determine MS outcome. Disease trajectories with and without biennial MS are extrapolated for each age cohort using the available data and knowledge on MS. The competing mortality is randomly generated for each age cohort with and without MS for a follow-up period of 20 years. Analyses of the modeled cohorts describe incremental change for each year, quantifying the changing benefits of MS. With increasing age, the proportion of tumor-independent mortality before and with metastatic disease increases and the benefit decreases. The simulations with 21 studies on the age interval 40–80 years provide four parameters to determine the benefits and costs of MS: The number of prevented deaths, required mammography screening exams (MSE) and their costs, life-years gained, and the required MSEs. If one additional MSE is offered for age groups 48/70 years, this will result in 311/320 prevented breast cancer (BC) deaths with 1742/1494 required MSEs or 8784/4168 life-years gained with 64/140 required MSEs. A rational cutoff cannot be quantified. The mortality effect of MS between 40 and 80 years is quantified in 21 steps using two metrics, number of MSEs per tumor-related mortality prevented and per life-year gained. This provides a decision support for stepwise expansions. Given this real-world evidence no rational age cutoffs for MS becomes evident. A society has to decide which MS costs, including side effects of MS for women who remain BC-free, it is willing and able to accept in order to reduce breast cancer mortality.

Prevalence of women with breast implants in Sweden: a study based on the population-based mammography screening programme.

Knowledge about the prevalence of women with breast implants is paramount in calculations of risks and in estimations of effects on screening and breast cancer treatment. Most of the estimations of prevalence made to date are rough and often based on sales data. The main aim of this study was to calculate the prevalence of breast implants in Swedish women. The secondary aim was to investigate if it is feasible to establish the occurrence of breast implants with the help of the public mammography screening programme, in a country with a publicly funded welfare-type healthcare system and with a clear documentation of screening. Information on implants was prospectively collected from all screening attendants from 1st of February 2022 to 1st of August 2022 based on a question from the radiographer to the woman and later verified on the mammogram. During the study period 4,639 women were screened, of which 182 had implants (3.9%). The frequency varies between 1.6 and 6.4% in different age groups. The prevalence of breast implants in Swedish women is estimated to be around 4%. The population-based mammography screening programme in countries with a publicly funded welfare-type healthcare system and a clear documentation of mammography screening attendance, seems to be a feasible way to establish the prevalence of breast implants in the population. The large number of women with breast implants warrants further studies regarding the best diagnostic and treatment alternatives for this group. Pre-registration: ClinicalTrials.Gov identifier NCT05222100.

German mammography screening program: program sensitivity between 2010 and 2016 estimated based on German health claims data

BackgroundProgram sensitivity is a key quality indicator for mammography screening programs (MSP). Estimating program sensitivity usually requires a linkage of screening and cancer registry data. For the German MSP, such data linkage-based estimates have only been reported for two out of 16 federal states. We aimed to explore the potential of estimating program sensitivity for the German MSP based on information available in health claims data.MethodsWe used data from the second-largest statutory health insurance fund in Germany, BARMER (~ 9 million members all over Germany). We included women aged 50 to 69 years with a non-initial screening mammography between 2010 and 2016 and followed them up for two years. We estimated the rate of screen-detected and interval cancers as well as program sensitivity.ResultsPer year, we included 212,400 to 303,667 women (mean age: 60–61 years). Overall, 1,992,287 non-initial MSP screening examinations conducted in these women between 2010 and 2016 were considered for the analyses. Age-standardized program sensitivity ranged between 69.9% [95% CI: 67.3–72.0%] and 71.7% [95% CI: 69.5-73.9%] during the study period. Per 1,000 non-initial screening examinations, the rate of screen-detected breast cancer ranged between 4.6 and 5.3, and the rate of interval breast cancer rates ranged between 0.6 and 0.8 for the first and between 1.3 and 1.4 for the second year after screening.ConclusionsOur results were plausible and consistent with quality indicators estimated for the German MSP based on data linkage and thus support the value of German health claims data in this regard. The quality indicators estimated in our study are in line with levels expected according to European Guidelines.

German mammography screening program: adherence, characteristics of (non-)participants and utilization of non-screening mammography—a longitudinal analysis

BackgroundIn Germany, all women aged 50–69 have been invited to biennial mammography screening since 2009. We aimed to assess longitudinal adherence over ten years in women aged 50 in 2009 and characterize the different adherence groups.MethodsUsing the German Pharmacoepidemiological Research Database (GePaRD, ~ 20% of the German population), we included women aged 50 in 2009 (baseline) with continuous health insurance coverage and without breast cancer or in-situ-carcinoma. We followed them until age 59 and categorized them according to mammography screening participation into the following groups: never, 1–2, 3–4, 5–6 times. We characterized these groups, inter alia, regarding the use of other preventive measures, non-screening mammography (i.e., mammography outside the organized screening program) and menopausal hormone therapy.ResultsOverall, 82,666 women were included. Of these, 27.6% never participated in the screening program, 15.1% participated 1–2 times, 31.7% participated 3–4 times and 25.6% participated regularly (5–6 times). Among regular participants, 91% utilized other preventive measures (e.g., cervical cancer screening, general health checkup) before baseline as compared to 66% among non-participants. Menopausal hormone therapy was least common among non-participants (11% vs. 18% among regular participants). Among non-participants, the proportions using ≥ 1, ≥ 2, and ≥ 3 non-screening mammographies between age 50–59 were 25%, 18%, and 15%, respectively.ConclusionsUsing a large cohort based on claims data, this study provides novel insights into longitudinal adherence to the mammography screening program and the use of mammography outside of the program in Germany. Between age 50–59, 57% of eligible women participated at least three times in the German mammography screening program and 28% (~ 3 in 10 women) never participated. Among non-participants, 15% had at least three non-screening mammographies during this period, indicating potential gray screening. Participants more often utilized other preventive measures as compared to non-participants.

Take a break: should breaks be enforced during digital breast tomosynthesis reading sessions?

ObjectivesDigital breast tomosynthesis (DBT) can improve diagnostic accuracy compared to 2D mammography, but DBT reporting is time-consuming and potentially more fatiguing. Changes in diagnostic accuracy and subjective and objective fatigue were evaluated over a DBT reporting session, and the impact of taking a reporting break was assessed.Materials and methodsForty-five National Health Service (NHS) mammography readers from 6 hospitals read a cancer-enriched set of 40 DBT cases whilst eye tracked in this prospective cohort study, from December 2020 to April 2022. Eye-blink metrics were assessed as objective fatigue measures. Twenty-one readers had a reporting break, 24 did not. Subjective fatigue questionnaires were completed before and after the session. Diagnostic accuracy and subjective and objective fatigue measures were compared between the cohorts using parametric and non-parametric significance testing.ResultsReaders had on average 10 years post-training breast screening experience and took just under 2 h (105.8 min) to report all cases. Readers without a break reported greater levels of subjective fatigue (44% vs. 33%, p = 0.04), which related to greater objective fatigue: an increased average blink duration (296 ms vs. 286 ms, p < 0.001) and a reduced eye-opening velocity (76 mm/s vs. 82 mm/s, p < 0.001). Objective fatigue increased as the trial progressed for the no break cohort only (ps < 0.001). No difference was identified in diagnostic accuracy between the groups (accuracy: 87% vs. 87%, p = 0.92).ConclusionsImplementing a break during a 2-h DBT reporting session resulted in lower levels of subjective and objective fatigue. Breaks did not impact diagnostic accuracy, which may be related to the extensive experience of the readers.Clinical relevance statementDBT is being incorporated into many mammography screening programmes. Recognising that reporting breaks are required when reading large volumes of DBT studies ensures this can be factored in when setting up reading sessions.Trial registrationClinical trials registration number: NCT03733106Key Points• Use of digital breast tomosynthesis (DBT) in breast screening programmes can cause significant reader fatigue.• The effectiveness of incorporating reading breaks into DBT reporting sessions, to reduce mammography reader fatigue, was investigated using eye tracking.• Integrating breaks into DBT reporting sessions reduced reader fatigue; however, diagnostic accuracy was unaffected.