Screen-detected Breast Cancer Research Articles

Age-specific differences in breast cancer treatment between screen-detected and non-screen-detected breast cancers in women aged 40-74 years at diagnosis in Sweden 2008-2017.

We have recently demonstrated that screen-detected invasive breast cancers had more favourable tumour characteristics than non-screen-detected. The objective of the study was to analyse differences in breast cancer treatment between screen-detected and non-screen-detected cases by age at diagnosis, with and without adjustment for tumour (T) and nodal (N) status, within a nationwide, population-based mammography screening programme utilising register data. Data spanning 2008-2017 were collected from the National Quality Register for Breast Cancer. Multivariable logistic regression analysis was used to estimate odds ratios and 95% confidence intervals for treatment disparities between screen-detected and non-screen-detected breast cancer. Among 46,481 women diagnosed with invasive breast cancer aged 40-74 and invited for mammography screening, significant differences in treatment were observed. Screen-detected cases showed higher likelihoods of partial mastectomy compared to mastectomy, endocrine therapy, and radiotherapy, whereas chemotherapy and antibody therapy were less likely compared to non-screen-detected cases. However, when adjusting for surgery type, screen-detected cases showed lower likelihoods of radiotherapy. Age at diagnosis significantly influenced treatment odds ratios, with interactions observed for all treatments except radiotherapy adjusted for surgery. Differences increased with age, except for endocrine therapy. Radiotherapy adjusted for surgery type showed no age-related interaction. Adjusting for T and N did not alter these patterns. In general, screen-detected cases received less aggressive treatment, such as mastectomy, chemotherapy, and antibody therapy, compared to non-screen-detected cases. Disparities increased with age, except for endocrine therapy and radiotherapy adjusted for surgery. Differences persisted after adjusting for T and N, suggesting that these factors cannot solely explain the results.

Genetic landscape of interval and screen detected breast cancer

Interval breast cancers (IBCs) are cancers diagnosed between screening episodes. Understanding the biological differences between IBCs and screen-detected breast-cancers (SDBCs) has the potential to improve mammographic screening and patient management. We analysed and compared the genomic landscape of 288 IBCs and 473 SDBCs by whole genome sequencing of paired tumour-normal patient samples collected as part of the UK 100,000 Genomes Project. Compared to SDBCs, IBCs were more likely to be lobular, higher grade, and triple negative. A more aggressive clinical phenotype was reflected in IBCs displaying features of genomic instability including a higher mutation rate and number of chromosomal structural abnormalities, defective homologous recombination and TP53 mutations. We did not however, find evidence to indicate that IBCs are associated with a significantly different immune response. While IBCs do not represent a unique molecular class of invasive breast cancer they exhibit a more aggressive phenotype, which is likely to be a consequence of the timing of tumour initiation. This information is relevant both with respect to treatment as well as informing the screening interval for mammography.

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.

Menopausal hormone therapy and breast cancer risk: a population-based cohort study of 1.3 million women in Norway

BackgroundIt is important to monitor the association between menopausal hormone therapy (HT) use and breast cancer (BC) risk with contemporary estimates, and specifically focus on HT types and new drugs.MethodsWe estimated hazard ratios (HR) of BC risk according to HT type, administration route and individual drugs, overall and stratified by body mass index (BMI), molecular subtype and detection mode, with non-HT use as reference.ResultsWe included 1,275,783 women, 45+ years, followed from 2004, for a median of 12.7 years. Oral oestrogen combined with daily progestin was associated with the highest risk of BC (HR 2.42, 95% confidence interval (CI) 2.31–2.54), with drug-specific HRs ranging from Cliovelle®: 1.63 (95% CI 1.35–1.96) to Kliogest®: 2.67 (2.37–3.00). Vaginal oestradiol was not associated with BC risk. HT use was more strongly associated with luminal A cancer (HR 1.97, 95% CI 1.86–2.09) than other molecular subtypes, and more strongly with interval (HR 2.00, 95% CI: 1.83–2.30) than screen-detected (HR 1.33, 95% CI 1.26–1.41) BC in women 50–71 years. HRs for HT use decreased with increasing BMI.ConclusionsThe use of oral and transdermal HT was associated with an increased risk of BC. The associations varied according to HT type, individual drugs, molecular subtype, detection mode and BMI.

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 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 PO4-08-06: Causal Relationships and Familial Aggregation of Mammogram Risk Scores: Insights from Breast Cancer in Twins and Families

Abstract Background: Mammogram risk scores based on texture and density, determined by brightness thresholds, are associated with breast cancer risk differently and could reveal distinct information about breast cancer risk. This study aimed to investigate the causal relationships between these intercorrelated risk scores and the familial aggregation of a texture-based mammogram measure, shedding light on the relevance to breast cancer aetiology. Methods: We analysed data from the Australian Mammographic Density Twins and Sisters Study, including 3195 breast-cancer-free women from 1519 families. The dataset comprised 527 pairs of monozygotic (MZ) twins, 271 pairs of dizygotic (DZ) twins, and 1599 sisters. The average age at mammography for sister pairs ranged from 40 to 70 years. Mammogram risk scores based on texture (named Cirrus) and three density-defined areas (light, bright, and brightest) that were spatially independent were generated. The Inference about Causation from Examination of Familial Confounding (ICE FALCON) method was employed for causal inference. Familial aggregation and the variance of Cirrus were assessed as a function of age using a multivariate normal model for pedigree analysis. The classic twin model was employed but allowing for varying shared environmental effects among different sister pairs. The single-nucleotide polymorphism (SNP)-based heritability was estimated using genetic variants from both closely and distantly related individuals. Model fits were compared using likelihood ratio tests and the Akaike Information Criterion. Results: Causal analysis using ICE FALCON revealed significant positive causal effects, with Cirrus, light areas, and bright areas influencing the brightest areas (accounting for 34%, 55%, and 85% of the associations, respectively). Similarly, light areas and bright areas demonstrated causal effects on Cirrus (accounting for 37% and 28% of the associations, respectively). No age-related differences in familial correlations or Cirrus variance were found for women aged 40 to 70 years. Familial correlations were estimated at 0.51 (0.03) for MZ pairs and 0.16 (0.03) for combined DZ and non-twin sister pairs, with no significant difference between DZ and non-twin sister pairs (P=0.3). Additive genetic effects accounted for up to 32% (5%) of the variance, consistent with SNP-based heritability estimates of 36% (12%). MZ-specific environmental effects contributed to at least 20% (3%), while shared environmental effects for DZ and non-twin sibling pairs accounted for less than 40% of that for MZ pairs. Conclusion: In a mammogram, the lighter (less dense) areas causally influence the brightest (highly dense) areas, including through textural features. These causal relationships provide insights into the relative importance of different mammogram features in breast cancer aetiology. For example, the brightest areas are more aetiologically important for screen-detected breast cancer, while the light areas are more aetiologically important for interval breast cancer. Additionally, specific textural features capture aetiologically independent breast cancer risk information from dense areas. We also confirm the partial heritability of Cirrus, the texture-based mammogram measure, substantially influenced by environmental factors (familial and non-familial). As well as genetic factors, Cirrus could be determined by factors operating at times of life when MZ pairs share their environments to a greater extent than do DZ and non-twin sisters, starting in utero and prior to adulthood, and remaining constant thereafter. These insights from twin and family data enhance our understanding of mammogram risk scores and their implications for breast cancer risk assessment. Citation Format: Zhoufeng Ye, Shuai Li, Gill Dite, Tuong Nguyen, Robert MacInnis, John Hopper. Causal Relationships and Familial Aggregation of Mammogram Risk Scores: Insights from Breast Cancer in Twins and Families [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 PO4-08-06.

A comparative analysis of risk factor associations with interval and screen-detected breast cancers: A large UK prospective study.

The associations of certain factors, such as age and menopausal hormone therapy, with breast cancer risk are known to differ for interval and screen-detected cancers. However, the extent to which associations of other established breast cancer risk factors differ by mode of detection is unclear. We investigated associations of a wide range of risk factors using data from a large UK cohort with linkage to the National Health Service Breast Screening Programme, cancer registration, and other health records. We used Cox regression to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs) for associations between risk factors and breast cancer risk. A total of 9421 screen-detected and 5166 interval cancers were diagnosed in 517,555 women who were followed for an average of 9.72 years. We observed the following differences in risk factor associations by mode of detection: greater body mass index (BMI) was associated with a smaller increased risk of interval (RR per 5 unit increase 1.07, 95% CI 1.03-1.11) than screen-detected cancer (RR 1.27, 1.23-1.30); having a first-degree family history was associated with a greater increased risk of interval (RR 1.81, 1.68-1.95) than screen-detected cancer (RR 1.52, 1.43-1.61); and having had previous breast surgery was associated with a greater increased risk of interval (RR 1.85, 1.72-1.99) than screen-detected cancer (RR 1.34, 1.26-1.42). As these differences in associations were relatively unchanged after adjustment for tumour grade, and are in line with the effects of these factors on mammographic density, they are likely to reflect the effects of these risk factors on screening sensitivity.

Mammographic features at primary breast cancer diagnosis in relation to recurrence-free survival

PurposeThe number of women living with breast cancer (BC) is increasing, and the efficacy of surveillance programs after BC treatment is essential. Identification of links between mammographic features and recurrence could help design follow up strategies, which may lead to earlier detection of recurrence. The aim of this study was to analyze associations between mammographic features at diagnosis and their potential association with recurrence-free survival (RFS). MethodsWomen with invasive BC in the prospective Malmö Diet and Cancer Study (n = 1116, 1991–2014) were assessed for locoregional and distant recurrences, with a median follow-up of 10.15 years. Of these, 34 women were excluded due to metastatic disease at diagnosis or missing recurrence data. Mammographic features (breast density [BI-RADS and clinical routine], tumor appearance, mode of detection) and tumor characteristics (tumor size, axillary lymph node involvement, histological grade) at diagnosis were registered. Associations were analyzed using Cox regression, yielding hazard ratios (HR) with 95 % confidence intervals (CI). ResultsOf the 1082 women, 265 (24.4 %) had recurrent disease. There was an association between high mammographic breast density at diagnosis and impaired RFS (adjusted HR 1.32 (0.98–1.79). In analyses limited to screen-detected BC, this association was stronger (adjusted HR 2.12 (1.35–3.32). There was no association between mammographic tumor appearance and recurrence. ConclusionRFS was impaired in women with high breast density compared to those with low density, especially among women with screen-detected BC. This study may lead to insights on mammographic features preceding BC recurrence, which could be used to tailor follow up strategies.

Impact of different age ranges on the benefits and harms of the breast cancer screening programme by the EU-TOPIA tool.

The recommendation for the implementation of mammography screening in women aged 45-49 and 70-74 is conditional with moderate certainty of the evidence. The aim of this study is to simulate the long-term outcomes (2020-50) of using different age range scenarios in the breast cancer screening programme of the Valencia Region (Spain), considering different programme participation rates. Three age range scenarios (S) were simulated with the EU-TOPIA tool, considering a biennial screening interval: S1, 45-69 years old (y); S2, 50-69 y and S3, 45-74 y. Simulations were performed for four participation rates: A = current participation (72.7%), B = +5%, C = +10% and D = +20%. Considered benefits: number (N°) of in situ and invasive breast cancers (BC) (screen vs. clinically detected), N° of BC deaths and % BC mortality reduction. Considered harms: N° of false positives (FP) and % overdiagnosis. The results showed that BC mortality decreased in all scenarios, being higher in S3A (32.2%) than S1A (30.6%) and S2A (27.9%). Harms decreased in S2A vs. S1A (N° FP: 236 vs. 423, overdiagnosis: 4.9% vs. 5.0%) but also benefits (BC mortality reduction: 27.9% vs. 30.6%, N° screen-detected invasive BC 15/28 vs. 18/25). In S3A vs. S1A, an increase in benefits was observed (BC mortality reduction: 32.2% vs. 30.6%), N° screen-detected in situ B: 5/2 vs. 4/3), but also in harms (N° FP: 460 vs. 423, overdiagnosis: 5.8% vs. 5.0%). Similar trends were observed with increased participation. As the age range increases, so does not only the reduction in BC mortality, but also the probability of FP and overdiagnosis.

Systematic review and meta-analysis of prognostic characteristics for breast cancers in populations with digital vs film mammography indicate the transition may have increased both early detection and overdiagnosis

ObjectivesFilm mammography has been replaced by digital mammography in breast screening programs globally. This led to a small increase in the rate of detection, but whether the detection of clinically important cancers increased is uncertain. We aimed to assess the impact on tumor characteristics of screen-detected and interval breast cancers. Study Design and SettingWe searched seven databases from inception to October 08, 2023, for publications comparing film and digital mammography within the same population of asymptomatic women at population (average) risk of breast cancer. We recorded reported tumor characteristics and assessed risk of bias using the Risk Of Bias In Non-randomised Studies - of Interventions tool. We synthesized results using meta-analyses of random effects. ResultsEighteen studies were included in the analysis from 8 countries, including 11,592,225 screening examinations (8,117,781 film; 3,474,444 digital). There were no differences in tumor size, morphology, grade, node status, receptor status, or stage in the pooled differences for screen-detected and interval invasive cancer tumor characteristics. There were statistically significant increases in screen-detected ductal carcinoma in situ (DCIS) across all grades: 0.05 (0.00–0.11), 0.14 (0.05–0.22), and 0.19 (0.05–0.33) per 1000 screens for low, intermediate, and high-grade DCIS, respectively. There were similar (non-statistically significant) increases in screen-detected invasive cancer across all grades. ConclusionThe increased detection of all grades of DCIS and invasive cancer may indicate both increased early detection of more aggressive disease and increased overdiagnosis.

Lead-Time Corrected Effect on Breast Cancer Survival in Germany by Mode of Detection.

(1) Background: Screen-detected breast cancer patients tend to have better survival than patients diagnosed with symptomatic cancer. The main driver of improved survival in screen-detected cancer is detection at earlier stage. An important bias is introduced by lead time, i.e., the time span by which the diagnosis has been advanced by screening. We examine whether there is a remaining survival difference that could be attributable to mode of detection, for example, because of higher quality of care. (2) Methods: Women with a breast cancer (BC) diagnosis in 2000-2022 were included from a population-based cancer registry from Schleswig-Holstein, Germany, which also registers the mode of cancer detection. Mammography screening was available from 2005 onwards. We compared the survival for BC detected by screening with symptomatic BC detection using Kaplan-Meier, unadjusted Cox regressions, and Cox regressions adjusted for age, grading, and UICC stage. Correction for lead time bias was carried out by assuming an exponential distribution of the period during which the tumor is asymptomatic but screen-detectable (sojourn time). We used a common estimate and two recently published estimates of sojourn times. (3) Results: The analysis included 32,169 women. Survival for symptomatic BC was lower than for screen-detected BC (hazard ratio (HR): 0.23, 95% confidence interval (CI): 0.21-0.25). Adjustment for prognostic factors and lead time bias with the commonly used sojourn time resulted in an HR of 0.84 (CI: 0.75-0.94). Using different sojourn times resulted in an HR of 0.73 to 0.90. (4) Conclusions: Survival for symptomatic BC was only one quarter of screen-detected tumors, which is obviously biased. After adjustment for lead-time bias and prognostic variables, including UICC stage, survival was 27% to 10% better for screen-detected BC, which might be attributed to BC screening. Although this result fits quite well with published results for other countries with BC screening, further sources for residual confounding (e.g., self-selection) cannot be ruled out.

Examining the impact of COVID-19 disruptions on population-based breast cancer screening in Ireland.

Many population-based breast screening programmes temporarily suspended routine screening following the COVID-19 pandemic onset. This study aimed to describe screening mammography utilisation and the pattern of screen-detected breast cancer diagnoses following COVID-19-related screening disruptions in Ireland. Using anonymous aggregate data from women invited for routine screening, three time periods were examined: (1) January-December 2019, (2) January-December 2020, and (3) January-December 2021. Descriptive statistics were conducted and comparisons between groups were performed using chi-square tests. In 2020, screening mammography capacity fell by 67.1% compared to 2019; recovering to 75% of mammograms performed in 2019, during 2021. Compared to 2019, for screen-detected invasive breast cancers, a reduction in Grade 1 (14.2% vs. 17.2%) and Grade 2 tumours (53.4% vs. 58.0%) and an increase in Grade 3 tumours (32.4% vs. 24.8%) was observed in 2020 (p = 0.03); whereas an increase in Grade 2 tumours (63.3% vs. 58.0%) and a reduction in Grade 3 tumours (19.6% vs. 24.8%) was found in 2021 (p = 0.02). No changes in oestrogen receptor-positive or nodal-positive diagnoses were observed; however the proportion of oestrogen/progesterone receptor-positive breast cancers significantly increased in 2020 (76.2%; p < 0.01) and 2021 (78.7%; p < 0.001) compared to 2019 (67.8%). These findings demonstrate signs of a grade change for screen-detected invasive breast cancers early in the pandemic, with recovery evident in 2021, and without an increase in nodal positivity. Future studies are needed to determine the COVID-19 impact on long-term breast cancer outcomes including mortality.

Long-term trends in incidence, characteristics and prognosis of screen-detected and interval cancers in women participating in the Dutch breast cancerscreening programme.

No studies are available in which changes over time in characteristics and prognosis of patients with interval breast cancers (ICs) and screen-detected breast cancers (SDCs) have been compared. The aim was to study these trends between 1995 and 2018. All women with invasive SDCs (N = 4290) and ICs (N = 1352), diagnosed in a southern mammography screening region in the Netherlands, were included and followed until date of death or 31 December 2022. The 5-year overall survival rate of women with SDCs increased from 91.4% for those diagnosed in 1995-1999 to 95.0% for those diagnosed in 2013-2018 (P < 0.001), and from 74.8 to 91.6% (P < 0.001) in the same periods for those with ICs. A similar trend was observed for the 10-year survival rates. After adjustment for changes in tumour characteristics, the hazard ratio (HR) for overall survival was 0.47 (95% confidence interval (CI): 0.38-0.59) for women with SDCs diagnosed in the period 2013-2018, compared to the women diagnosed in the period 1995-1999. For the women with ICs this HR was 0.27 (95% CI: 0.19-0.40). The prognosis of women with ICs has improved rapidly since 1995 and is now almost similar to that of women with SDCs.

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.

Comprehensive Inherited Risk Estimation for Risk-Based Breast Cancer Screening in Women.

Family history (FH) and pathogenic variants (PVs) are used for guiding risk surveillance in selected high-risk women but little is known about their impact for breast cancer screening on population level. In addition, polygenic risk scores (PRSs) have been shown to efficiently stratify breast cancer risk through combining information about common genetic factors into one measure. In longitudinal real-life data, we evaluate PRS, FH, and PVs for stratified screening. Using FinnGen (N = 117,252), linked to the Mass Screening Registry for breast cancer (1992-2019; nationwide organized biennial screening for age 50-69 years), we assessed the screening performance of a breast cancer PRS and compared its performance with FH of breast cancer and PVs in moderate- (CHEK2)- to high-risk (PALB2) susceptibility genes. Effect sizes for FH, PVs, and high PRS (>90th percentile) were comparable in screening-aged women, with similar implications for shifting age at screening onset. A high PRS identified women more likely to be diagnosed with breast cancer after a positive screening finding (positive predictive value [PPV], 39.5% [95% CI, 37.6 to 41.5]). Combinations of risk factors increased the PPVs up to 45% to 50%. A high PRS conferred an elevated risk of interval breast cancer (hazard ratio [HR], 2.78 [95% CI, 2.00 to 3.86] at age 50 years; HR, 2.48 [95% CI, 1.67 to 3.70] at age 60 years), and women with a low PRS (<10th percentile) had a low risk for both interval- and screen-detected breast cancers. Using real-life screening data, this study demonstrates the effectiveness of a breast cancer PRS for risk stratification, alone and combined with FH and PVs. Further research is required to evaluate their impact in a prospective risk-stratified screening program, including cost-effectiveness.

Breast cancer-specific survival among immigrants and non-immigrants invited to BreastScreen Norway

IntroductionWe have previously shown that immigrants have lower attendance in BreastScreen Norway than non-immigrants and that non-Western immigrants have lower incidence of breast cancer, but more advanced disease. PurposeTo compare breast cancer-specific survival for immigrants versus non-immigrants diagnosed with screen-detected or symptomatic breast cancer. Material and methodsWe analyzed data from 28,320 women aged 50–69 diagnosed with breast cancer after being invited to BreastScreen Norway. We divided women into three groups; non-immigrants, immigrants from Western countries and immigrants from non-Western countries. We stratified our analyses according to detection mode (screen-detected breast cancer, interval cancer and cancer detected outside screening), and used cox regression to model the association between immigrants/non-immigrants and time to breast cancer death. ResultsAmong screen-detected breast cancers, 28.7% were histologic grade 3 among immigrants from non-Western countries compared to 21.3% among non-immigrants. Interval cancers and cancers detected outside screening had larger tumor diameter and a higher percentage were histologic grade 3 and lymph node positive among immigrants from non-Western countries compared to non-immigrants. Hazard ratio (95% confidence interval) adjusted for age and year of diagnosis for time to breast cancer death compared to non-immigrants was 0.70 (0.39–1.27) for immigrants from Western countries and 0.52 (0.23–1.17) for immigrants from non-Western countries. ConclusionDespite more advanced histopathological tumor characteristics among immigrants from non-Western countries compared to non-immigrants, we did not observe statistically significant differences in breast-cancer specific survival between the two groups. Keeping in mind the low number of breast cancer deaths and possible overestimation of survival among immigrants, this might imply that equity in outcome can be achieved through adequate follow-up and treatment despite inequal access.

Benefits and harms of breast cancer screening revisited: a large, retrospective cross-sectional study quantifying treatment intensity in women with screen-detected versus non-screen-detected cancer in Australia and New Zealand

ObjectivesNon-mortality benefits of breast cancer screening are rarely considered in assessments of benefits versus harms. This study aims to estimate the rate of overdiagnosis in women with screen-detected breast cancer...

P12 Screen-Detected Breast Cancers Have Improved 5-Year Disease Free Interval Compared to Interval and Non-Screen-Related Breast Cancer, Taking Lead Time into Account

P12 Screen-Detected Breast Cancers Have Improved 5-Year Disease Free Interval Compared to Interval and Non-Screen-Related Breast Cancer, Taking Lead Time into Account

Saliency of breast lesions in breast cancer detection using artificial intelligence

The analysis of mammograms using artificial intelligence (AI) has shown great potential for assisting breast cancer screening. We use saliency maps to study the role of breast lesions in the decision-making process of AI systems for breast cancer detection in screening mammograms. We retrospectively collected mammograms from 191 women with screen-detected breast cancer and 191 healthy controls matched by age and mammographic system. Two radiologists manually segmented the breast lesions in the mammograms from CC and MLO views. We estimated the detection performance of four deep learning-based AI systems using the area under the ROC curve (AUC) with a 95% confidence interval (CI). We used automatic thresholding on saliency maps from the AI systems to identify the areas of interest on the mammograms. Finally, we measured the overlap between these areas of interest and the segmented breast lesions using Dice’s similarity coefficient (DSC). The detection performance of the AI systems ranged from low to moderate (AUCs from 0.525 to 0.694). The overlap between the areas of interest and the breast lesions was low for all the studied methods (median DSC from 4.2% to 38.0%). The AI system with the highest cancer detection performance (AUC = 0.694, CI 0.662–0.726) showed the lowest overlap (DSC = 4.2%) with breast lesions. The areas of interest found by saliency analysis of the AI systems showed poor overlap with breast lesions. These results suggest that AI systems with the highest performance do not solely rely on localized breast lesions for their decision-making in cancer detection; rather, they incorporate information from large image regions. This work contributes to the understanding of the role of breast lesions in cancer detection using AI.