Appropriation 2011.0007 Enacted

Objectives: Women diagnosed with breast cancer are offered treatment and therapy based on tumor characteristics, including tumor diameter. There is scarce knowledge whether tumor diameter is accurately reported, or whether it is unconsciously rounded to the nearest half-centimeter (terminal digit preference). This study aimed to assess the precision (number of digits) of breast cancer tumor diameters and whether they are affected by terminal digit preference. Furthermore, we aimed to assess the agreement between mammographic and histopathologic tumor diameter measurements. Material and Methods: This national registry study included reported mammographic and registered histopathologic tumor diameter information from the Cancer Registry of Norway for invasive breast cancers diagnosed during 2012–2016. Terminal digit preference was assessed using histograms. Agreement between mammographic and histopathologic measurements was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman plots. Results: Mammographic, histopathologic, or both tumor measurements were available for 7792, 13,541 and 6865 cases, respectively. All mammographic and 97.2% of histopathologic tumor diameters were recorded using whole mm. Terminal digits of zero or five were observed among 38.7% and 34.8% of mammographic and histopathologic measurements, respectively. There was moderate agreement between the two measurement methods (ICC = 0.52, 95% CI: 0.50–0.53). On average, mammographic measurements were 1.26 mm larger (95% limits of agreement: −22.29–24.73) than histopathologic measurements. This difference increased with increasing tumor size. Conclusion: Terminal digit preference was evident among breast cancer tumor diameters in this nationwide study. Further studies are needed to investigate the potential extent of under-staging and under-treatment resulting from this measurement error

Breast cancer mortality in participants of the Norwegian Breast Cancer Screening Program

BACKGROUND The Norwegian Breast Cancer Screening Program started in 1996. To the authors' knowledge, this is the first report using individual-based data on invitation and participation to analyze breast cancer mortality among screened and nonscreened women in the program. METHODS Information on dates of invitation, attendance, breast cancer diagnosis, emigration, death, and cause of death was linked by using unique 11-digit personal identification numbers assigned all inhabitants of Norway at birth or immigration. In total, 699,628 women ages 50 to 69 years without prior a diagnosis of breast cancer were invited to the program from 1996 to 2009 and were followed for breast cancer through 2009 and death through 2010. Incidence-based breast cancer mortality rate ratios (MRRs) were compared between the screened and nonscreened cohorts using a Poisson regression model. The MRRs were adjusted for calendar period, attained age, years since inclusion in the cohorts, and self-selection bias. RESULTS The crude breast cancer mortality rate was 20.7 per 100,000 women-years for the screened cohort compared with 39.7 per 100,000 women-years for the nonscreened cohort, resulting in an MRR of 0.52 (95% confidence interval, 0.47-0.59). The mortality reduction associated with attendance in the program was 43% (MRR, 0.57; 95% confidence interval, 0.51-0.64) after adjusting for calendar period, attained age, years after inclusion in the cohort, and self-selection bias. CONCLUSIONS After 15 years of follow-up, a 43% reduction in mortality was observed among women who attended the national mammographic screening program in Norway

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

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

Detection and significance of small and low proliferation breast cancer

Objectives To determine the frequency and discuss possible implications of early breast cancer with particularly good prognosis and defined by tumor diameter and cell proliferation. Setting Detection of small and slowly growing tumors presents a challenge in breast cancer management, due to the risk of over-treatment. Here, we attempted to define a group of such tumors by combining small diameter (≤10 mm, T1ab tumors) with low tumor cell proliferation (≤10% Ki67 expression rate). These tumors were termed small low proliferation cancers (SLPC). Methods Two population-based cohorts were studied: a small research series (n = 534), and a nation-wide registry-based series of prospectively collected routine data (n = 8433). In the latter, we stratified by detection mode; screen-detected, interval, and breast cancers detected outside of screening. Patients were treated according to national guidelines at time of their diagnosis. For both cohorts, we compared tumor histopathology and risk of breast cancer death using a log-rank test for cases with SLPC versus non-SLPC. Results In the research series (median follow-up 151 months), the frequency of SLPC was 10% (54/534), with one breast cancer death compared with 78 among the remaining 480 cases of non-SLPC (p = 0.008). In the registry series (median follow-up 42 months), the frequency of SLPC was 10% (854/8433), with five deaths compared to 187 among the remaining 7579 cases (p = 0.0004). Conclusions SLPC was associated with very low risk of breast cancer death. Prospective randomized trials are needed to clarify whether less aggressive treatment could be a safe option for women with such early breast cancers.acceptedVersio

Mammographic screening in Sami speaking municipalities and a control group. Are early outcome measures influenced by ethnicity?

Objectives. Female citizens of Sami (the indigenous people of Norway) municipalities in northern Norway have a low risk of breast cancer. The objective of this study was to describe the attendance rate and outcome of the Norwegian Breast Cancer Screening Program (NBCSP) in the Sami-speaking municipalities and a control group. Study design. A retrospective registry-based study. Methods. The 8 municipalities included in the administration area of the Sami language law (Sami) were matched with a control group of 11 municipalities (non-Sami). Population data were accessed from Statistics Norway. Data regarding invitations and outcome in the NBCSP during the period 2001&#x2013;2010 was derived from the Cancer Registry of Norway (CRN). The NBCSP targets women aged 50&#x2013;69 years. Rates and percentages were compared using chi-square test with a p-value&#60;0.05 as statistical significant. Results. The attendance rate in the NBCSP was 78% in the Sami and 75% in the non-Sami population (p&#60; 0.01). The recall rates were 2.4 and 3.3% in the Sami and non-Sami population, respectively (p&#60;0.01). The rate of invasive screen detected cancer was not significantly lower in the Sami group (p=0.14). The percentage of all breast cancers detected in the NBCSP among the Sami (67%) was lower compared with the non-Sami population (86%, p=0.06). Conclusion. Despite a lower risk of breast cancer, the Sami attended the NBCSP more frequently than the control group. The recall and cancer detection rate was lower among the Sami compared with the non-Sami group

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

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

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

Prolonged screening interval due to the COVID-19 pandemic and its association with tumor characteristics and treatment; a register-based study from BreastScreen Norway

Objective: During the COVID-19 pandemic Norway had to suspend its national breast cancer screening program. We aimed to investigate the effect of the pandemic-induced suspension on the screening interval, and its subsequent association with the tumor characteristics and treatment of screen-detected (SDC) and interval breast cancer (IC). Methods: Information about women aged 50–69, participating in BreastScreen Norway, and diagnosed with a SDC (N = 3799) or IC (N = 1806) between 2018 and 2021 was extracted from the Cancer Registry of Norway. Logistic regression was used to investigate the association between COVID-19 induced prolonged screening intervals and tumor characteristics and treatment. Results: Women with a SDC and their last screening exam before the pandemic had a median screening interval of 24.0 months (interquartile range: 23.8–24.5), compared to 27.0 months (interquartile range: 25.8–28.5) for those with their last screening during the pandemic. The tumor characteristics and treatment of women with a SDC, last screening during the pandemic, and a screening interval of 29–31 months, did not differ from those of women with a SDC, last screening before the pandemic, and a screening interval of 23–25 months. ICs detected 24–31 months after screening, were more likely to be histological grade 3 compared to ICs detected 0–23 months after screening (odds ratio: 1.40, 95% confidence interval: 1.06–1.84). Conclusions: Pandemic-induced prolonged screening intervals were not associated with the tumor characteristics and treatment of SDCs, but did increase the risk of a histopathological grade 3 IC. This study provides insights into the possible effects of extending the screening interval