Possible strategies for use of artificial intelligence in screen-reading of mammograms, based on retrospective data from 122,969 screening examinations

Objectives Artificial intelligence (AI) has shown promising results when used on retrospective data from mammographic screening. However, few studies have explored the possible consequences of different strategies for combining AI and radiologists in screen-reading. Methods A total of 122,969 digital screening examinations performed between 2009 and 2018 in BreastScreen Norway were retrospectively processed by an AI system, which scored the examinations from 1 to 10; 1 indicated low suspicion of malignancy and 10 high suspicion. Results were merged with information about screening outcome and used to explore consensus, recall, and cancer detection for 11 different scenarios of combining AI and radiologists. Results Recall was 3.2%, screen-detected cancer 0.61% and interval cancer 0.17% after independent double reading and served as reference values. In a scenario where examinations with AI scores 1–5 were considered negative and 6–10 resulted in standard independent double reading, the estimated recall was 2.6% and screen-detected cancer 0.60%. When scores 1–9 were considered negative and score 10 double read, recall was 1.2% and screen-detected cancer 0.53%. In these two scenarios, potential rates of screen-detected cancer could be up to 0.63% and 0.56%, if the interval cancers selected for consensus were detected at screening. In the former scenario, screen-reading volume would be reduced by 50%, while the latter would reduce the volume by 90%. Conclusion Several theoretical scenarios with AI and radiologists have the potential to reduce the volume in screen-reading without affecting cancer detection substantially. Possible influence on recall and interval cancers must be evaluated in prospective studies. Key Points Different scenarios using artificial intelligence in combination with radiologists could reduce the screen-reading volume by 50% and result in a rate of screen-detected cancer ranging from 0.59% to 0.60%, compared to 0.61% after standard independent double reading The use of artificial intelligence in combination with radiologists has the potential to identify negative screening examinations with high precision in mammographic screening and to reduce the rate of interval cancer</li

Fatal and non-fatal breast cancers in women targeted by BreastScreen Norway: a cohort study

Background - Many breast cancer survivors experience anxiety related to dying from their disease even if it is detected at an early stage. We aimed to increase knowledge about fatal and non-fatal breast cancer by describing how histopathological tumour profiles and detection modes were associated with 10-year breast cancer-specific survival. Methods - This cohort study included data from women targeted by BreastScreen Norway (aged 50–69) and diagnosed with invasive breast cancer during 1996–2011. Breast cancer was classified as fatal if causing death within 10 years after diagnosis and non-fatal otherwise. We described histopathologic characteristics of fatal and non-fatal cancers, stratified by mode of detection. Recursive partitioning identified subgroups with differing survival profiles. Results - In total, 6.3% of 9954 screen-detected cancers (SDC) were fatal, as were 17.4% of 3205 interval cancers (IC) and 20.9% of 3237 cancers detected outside BreastScreen Norway. Four to five subgroups with differing survival profiles were identified within each detection mode. Women with lymph node-negative SDC or Grade 1–2, node-negative IC without distant metastases had the highest 10-year survival (95–96%). Conclusions - Two subgroups representing 53% of the cohort had excellent (95–96%) 10-year breast cancer-specific survival. Most women with SDC had excellent survival, as did nearly 40% of women diagnosed with IC

Mammographic features and risk of breast cancer death among women with invasive screen-detected cancer in BreastScreen Norway 1996–2020

Objectives We explored associations between mammographic features and risk of breast cancer death among women with small ( Methods We included data from 17,614 women diagnosed with invasive breast cancer as a result of participation in BreastScreen Norway, 1996–2020. Data on mammographic features (mass, spiculated mass, architectural distortion, asymmetric density, density with calcification and calcification alone), tumour diameter and cause of death was obtained from the Cancer Registry of Norway. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for breast cancer death by mammographic features using spiculated mass as reference, adjusting for age, tumour diameter and lymph node status. All analyses were dichotomised by tumour diameter (small versus large). Results Mean age at diagnosis was 60.8 (standard deviation, SD=5.8) for 10,160 women with small tumours and 60.0 (SD=5.8) years for 7454 women with large tumours. The number of breast cancer deaths was 299 and 634, respectively. Mean time from diagnosis to death was 8.7 (SD=5.0) years for women with small tumours and 7.2 (4.6) years for women with large tumours. Using spiculated mass as reference, adjusted HR for breast cancer death among women with small tumours was 2.48 (95% CI 1.67–3.68) for calcification alone, while HR for women with large tumours was 1.30 (95% CI 1.02–1.66) for density with calcifcation. Conclusions Small screen-detected invasive cancers presenting as calcification and large screen-detected cancers presenting as density with calcifcation were associated with the highest risk of breast cancer death. Clinical relevance statement Small tumours (<15 mm) presented as calcification alone and large tumours (≥ 15 mm) presented as density with calcification were associated with the highest risk of breast cancer death among women with screen-detected invasive breast cancer diagnosed 1996–2020

BreastScreen Norway – past, present, and future.

Mammografiprogrammet (engelsk: BreastScreen Norway) er det offentlige screeningprogrammet for brystkreft i Norge. Det startet som et pilotprosjekt i 1995 og ble gradvis landsdekkende frem til 2005. Programmet inviterer alle kvinner i alderen 50-69 år til mammografiscreening hvert annet år. Kreftregisteret har det administrative ansvaret for Mammografiprogrammet, mens screening skjer ved 30 screeningenheter knyttet til 17 spesialiserte brystsentre som har ansvar for diagnostikk, behandling og oppfølging. Mammografiprogrammet støtter seg på kunnskapsbaserte europeiske retningslinjer og anbefalinger. Programmet er stadig gjenstand for debatt, spesielt når det kommer til anslag for reduksjon i brystkreftdødelighet og overdiagnostikk, samt om kvinnene som inviteres tilbys tilstrekkelig informasjon til å ta et informert valg om deltagelse. Mammografiprogrammet har høy oppslutning, om lag 75% av de inviterte møter. Andelen som tilbakekalles etter screening er om lag 3,5%, mens andelen somfår diagnostisert brystkreft på bakgrunn av funn på screeningbildene errundt 0,6% av alle screenede. Målet med Mammografiprogrammet er å redusere dødeligheten av brystkreft gjennom tidlig diagnostikk. Det er også et mål å vedlikeholde og videreutvikle kvaliteten i programmet, og samtidig øke fordelene og redusere ulempene ved deltagelse. Gjennom studier undersøkes blant annet bruken av nye screeningteknikker som tomosyntese, og muligheter innenfor vurdering av mammografibilder med bruk av kunstig intelligens. Programmet ser også fremover med tanke på utvidelse av målgruppen og mer persontilpasset screening. Alle endringer i Mammografiprogrammet vil og bør være basert på tilgjengelig kunnskap og forskning. BreastScreen Norway targets women aged 50 to 69 years for mammography screening every other year. The program started as a pilot project in 1995, was gradually expanded and became nationwide from 2005. Internationally, the history of mammography screening started in the early 1960s, when the first randomized trial in New York began. At that time, breast cancer patients had poor survival. Now, more than 50 years later, organized mammography screening is a highly evaluated and quality assured health care service in Norway and internationally. In Norway, an essential part of building the nationwide screening program was the establishment of specialized breast centers, with a focus on efficient workflow, centralized professional competence, and multidisciplinary teamwork. Another key factor in the program is the invitation system, which is based on personal invitations with scheduled appointments automatically sent to all women in the target group. The invitation system facilitates regular participation regardless of where women live. The Norwegian model for breast screening is based on a centralized database and a shared IT system, which creates distinct opportunities for communication, quality assurance, and research. This ensures complete data and individual follow-up, and has been a successful model that is quite unique internationally. It is well known that the concept of mammography screening has spurred debates about its potential benefits and harms during the past decades, especially related to reduced breast cancer mortality and overdiagnosis, and the ethical question whether invited women are offered sufficient information to make an informed choice about participation. In recent years, international publications have strengthened the evidence for mammography screening. BreastScreen Norway relies on evidence-based European guidelines and recommendations, which conclude that there is sufficient evidence to support the benefits of mammography screening for women aged 50-69. BreastScreen Norway has a high attendance with an annual participation rate of 75%. The proportion of women recalled for further assessment is about 3.5%, while the rate of screen-detected cancer due to suspicious findings on mammography is around 0.6% of all screened. The main goal of BreastScreen Norway is to reduce breast cancer mortality through early detection. Another goal is to maintain and further develop the quality of the program, increase the benefits and reduce the harms of participating in the program. Through studies, the use of new screening methods, such as tomosynthesis, and new methods for assessing screening mammograms using artificial intelligence, are investigated. Important future perspectives of the program are related to expanding the age group and personalized screening. Changes in the program will and should be evidence-based and extensive research is needed to fill knowledge gaps before actions can be taken

The dose-response relationship of pre-menopausal alcohol consumption with age at menopause: a population study of 280 497 women in Norway

Background: Previous research suggests that alcohol consumption is associated with high age at menopause. Yet, knowledge about the dose– response relationship is inconsistent. Thus, we studied the pattern of the association of pre-menopausal alcohol consumption with age at natural menopause. Methods: We performed a retrospective population-based study using self-reported data from 280 497 women aged 50–69 years attending the Norwegian breast cancer screening programme (BreastScreen Norway) during 2006–15. Associations of weekly alcohol consumption between the age of 20 and 49 years with age at menopause were estimated as hazard ratios (HRs) using Cox proportional hazard models with restricted cubic splines to allow for non-linear associations. We adjusted for year and place of birth, number of childbirths, educational level, body mass index and smoking habits. Results: Mean age at natural menopause was 51.20 years (interquartile range: 49–54 years). The adjusted HR of reaching menopause was highest for women with no alcohol consumption (reference) and the HR decreased by alcohol consumption up to 50 grams per week (adjusted HR 0.87; 95% CI: 0.86–0.88). Above 50 grams, there was no further decrease in the HR of reaching menopause (P for non-linearity of <0.001). Conclusions: Women who did not consume alcohol were youngest at menopause. The lack of a dose–response association among alcohol consumers implies virtually no relation of alcohol consumption with age at menopause. Our findings may suggest that characteristics of the women who did not consume alcohol, not accounted for in the data analyses, explain their younger age at menopause

Sociodemographic factors, health indicators and lifestyle factors among participants in BreastScreen Norway 2006-2016 – a cohort profile

Purpose: To collect information on sociodemographic factors, health indicators, and lifestyle factors in women who attended the nationwide breast cancer-screening program, BreastScreen Norway, with the aim of investigating how these factors influence the risk of breast cancer, other cancer types, and cancer-related outcomes. Participants: The cohort data includes self-reported responses to questionnaires from 554,149 women aged 50- 69 years, who attended BreastScreen Norway during the data collection period, 2006-2016. Findings to date: Information about sociodemographic factors, health indicators, and lifestyle factors was collected for the current time and retrospectively back to birth. For the cohort, we have complete mammographic screening data, including information about 24,000 breast cancer cases and other cancer types from the Cancer Registry of Norway. These outcomes are aggregating continuously. Data from the cohort have been utilized in studies related to breast cancer and menopausal status. Future projects: Data will be utilized in studies related to tumour growth and risk of breast cancer as well as other cancer types, in addition to overall and cancer-specific death. Registration: The cohort profile is not registered in Clinical Trials

Overdiagnostikk – eksemplifisert ved mammografiscreening

Hovedmålsettingen med organisert mammografiscreening er å oppdage brystkreft i et tidlig stadium og dermed redusere sykelighet og dødelighet av sykdommen. En ulempe er overdiagnostikk. Verdens helseorganisasjons kreftforskningsinstitutt definerer overdiagnostikk i mammografiscreening som brystkreft som ikke ville blitt diagnostisert i kvinnens levetid dersom hun ikke hadde deltatt i screening. Vi kan ikke identifisere hvilke svulster som er overdiagnostiserte eller nøyaktig tallfeste omfanget av overdiagnostikk i mammografiscreening. Dersom vi analyserer data fra store grupper, kan vi gi et anslag på omfanget. Resultatet vil være avhengig av blant annet beregningsmetode, kontrollgruppe, oppfølgingstid, og hva slags type data som benyttes (individdata versus aggregattall). Selv om subtyper av brystkreft med ulik prognose kan defineres, kan vekstmønsteret innenfor samme subtype endres over tid, og det er derfor ikke mulig på diagnosetidspunktet å identifisere hvilke svulster som er overdiagnostiserte og ikke trenger behandling. Alle kvinner som får diagnostisert brystkreft tilbys derfor behandling. Begrepet overdiagnostikk er sammensatt og vanskelig å forstå. I noen sammenhenger brukes det som et paraplybegrep for ulike fenomener som for eksempel feildiagnoser, falskt positive screeningresultater eller overbehandling. Overdiagnostikk i mammografiscreening omfatter ikke feildiagnostikk eller falskt positive screeningresultater. Økt kunnskap i befolkningen og bruk av mer avanserte undersøkelsesteknikker gjør at flere brystkreftsvulster nå oppdages i et tidlig stadium og dermed øker risikoen for overdiagnostikk og overbehandling. Nye behandlingsmetoder reduserer brystkreftdødeligheten, også ved avansert sykdom, men ofte med bi- og seneffekter. Målet er mer presise screening- og diagnosemetoder, og mer persontilpasset behandling enn vi har i dag. Likevel er nok noe overdiagnostikk og overbehandling prisen vi må betale for å redde kvinner fra å dø av brystkreft.The goal of organized mammographic screening is early detection of breast cancer and thereby to reduce disease-specific morbidity and mortality. One disadvantage is overdiagnosis. The World Health Organization's International Agency for Research on Cancer defines overdiagnosis in mammographic screening as the diagnosis of a breast cancer as a result of screening that would not have been diagnosed in the woman’s lifetime if screening had not taken place. We cannot identify which tumors are overdiagnosed or accurately quantify the extent of overdiagnosis in mammographic screening. Analyzing data from large groups will give an estimate, but the result will depend, among other things, on the calculation method, control group, follow-up time, and type of data used (individual data versus aggregate numbers). Although subtypes of breast cancer with different prognosis can be defined, the growth patterns within the same subtype can change over time, and it is therefore not possible at the time of diagnosis to identify which tumours are overdiagnosed and do not require treatment. All women who are diagnosed with breast cancer are thus offered treatment. The term overdiagnosis is complex and difficult to understand. In some contexts, it is used as an umbrella term for various phenomena such as misdiagnosis, false positive screening results or overtreatment. Overdiagnosis in mammographic screening does not include misdiagnosis or false positives. Increased knowledge in the population and the use of more advanced examination techniques means that more breast cancer tumours are now detected at an early stage and thus increases the risk of overdiagnosis and overtreatment. New treatment methods reduce breast cancer mortality, also for advanced disease, but often at the cost of side and late effects of the treatment. The future goal is more precise screening and diagnostics, and more personalized treatment. Nevertheless, some overdiagnosis and overtreatment is probably the price we have to pay to save women from dying of breast cancer

Artificial intelligence in BreastScreen Norway: a retrospective analysis of a cancer-enriched sample including 1254 breast cancer cases

Objectives To compare results of selected performance measures in mammographic screening for an artifcial intelligence (AI) system versus independent double reading by radiologists. Methods In this retrospective study, we analyzed data from 949 screen-detected breast cancers, 305 interval cancers, and 13,646 negative examinations performed in BreastScreen Norway during the period from 2010 to 2018. An AI system scored the examinations from 1 to 10, based on the risk of malignancy. Results from the AI system were compared to screening results after independent double reading. AI score 10 was set as the threshold. The results were stratifed by mammographic density. Results A total of 92.7% of the screen-detected and 40.0% of the interval cancers had an AI score of 10. Among women with a negative screening outcome, 9.1% had an AI score of 10. For women with the highest breast density, the AI system scored 100% of the screen-detected cancers and 48.6% of the interval cancers with an AI score of 10, which resulted in a sensitivity of 80.9% for women with the highest breast density for the AI system, compared to 62.8% for independent double reading. For women with screen-detected cancers who had prior mammograms available, 41.9% had an AI score of 10 at the prior screening round. Conclusions The high proportion of cancers with an AI score of 10 indicates a promising performance of the AI system, particularly for women with dense breasts. Results on prior mammograms with AI score 10 illustrate the potential for earlier detection of breast cancers by using AI in screen-reading

Low-dose aspirin and risk of breast cancer: a Norwegian population-based cohort study of one million women

Several studies evaluated the association between aspirin use and risk of breast cancer (BC), with inconsistent results. We identifed women aged≥50 years residing in Norway between 2004 and 2018, and linked data from nationwide registries; including the Cancer Registry of Norway, the Norwegian Prescription Database, and national health surveys. We used Cox regression models to estimate the association between low-dose aspirin use and BC risk, overall and by BC characteristics, women’s age and body mass index (BMI), adjusting for sociodemographic factors and use of other medications. We included 1,083,629 women. During a median follow-up of 11.6 years, 257,442 (24%) women used aspirin, and 29,533 (3%) BCs occurred. For current use of aspirin, compared to never use, we found an indication of a reduced risk of oestrogen receptorpositive (ER+) BC (hazard ratio [HR]=0.96, 95% confdence interval [CI]: 0.92–1.00), but not ER-negative BC (HR=1.01, 95%CI: 0.90–1.13). The association with ER+BC was only found in women aged≥65 years (HR=0.95, 95%CI: 0.90–0.99), and became stronger as the duration of use increased (use of≥4 years HR=0.91, 95%CI: 0.85–0.98). BMI was available for 450,080 (42%) women. Current use of aspirin was associated with a reduced risk of ER+BC in women with BMI≥25 (HR=0.91, 95%CI: 0.83–0.99; HR=0.86, 95%CI: 0.75–0.97 for use of≥4 years), but not in women with BMI<25.Use of low-dose aspirin was associated with reduced risk of ER+BC, in particular in women aged≥65 years and overweight women

Effect of invitation letter in language of origin on screening attendance: randomised controlled trial in BreastScreen Norway

Objective To explore attendance at organised mammographic screening among immigrant groups that received an invitation letter and information leaflet (invitation) in their language of origin and Norwegian compared with Norwegian only. Design Randomised controlled trial. Setting Population based screening programme for breast cancer in Norway (BreastScreen Norway), which invites women aged 50-69 to two-view mammographic screening biennially. Participants All women invited to BreastScreen Norway in the study period April 2021 to June 2022 whose language of origin was Arabic (women born in Algeria, Egypt, Lebanon, Iraq, Palestine, Sudan, Syria, Tunisia, or Morocco), English (women born in the Philippines), Polish (women born in Poland), Somali (women born in Somalia), or Urdu (women born in Pakistan) (n=11347). Intervention The study group received an invitation to screening in their language of origin and in Norwegian, whereas the control group received an invitation in Norwegian only during the study period. Main outcome measure Attendance at BreastScreen Norway during the study period. Results Overall attendance was 46.5% (2642/5683) in the study group and 47.4% (2682/5664) in the control group. No statistical differences in attendance were observed after stratification by language of invitation, age at invitation, or years since immigration. Conclusions No difference in attendance was observed between immigrant women invited to BreastScreen Norway in their language of origin and in Norwegian compared with Norwegian only. Several barriers to cancer screening may exist among immigrants, and translating the invitation is probably only a part of a complex explanation