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

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

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

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

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

Mammographic features and screening outcome in a randomized controlled trial comparing digital breast tomosynthesis and digital mammography

Purpose To compare the distribution of mammographic features among women recalled for further assessment after screening with digital breast tomosynthesis (DBT) versus digital mammography (DM), and to assess associations between features and final outcome of the screening, including immunohistochemical subtypes of the tumour. Methods This randomized controlled trial was performed in Bergen, Norway, and included 28,749 women, of which 1015 were recalled due to mammographic findings. Mammographic features were classified according to a modified BI-RADS-scale. The distribution were compared using 95 % confidence intervals (CI). Results Asymmetry was the most common feature of all recalls, 24.3 % (108/444) for DBT and 38.9 % (222/571) for DM. Spiculated mass was most common for breast cancer after screening with DBT (36.8 %, 35/95, 95 %CI: 27.2−47.4) while calcifications (23.0 %, 20/87, 95 %CI: 14.6−33.2) was the most frequent after DM. Among women screened with DBT, 0.13 % (95 %CI: 0.08−0.21) had benign outcome after recall due to indistinct mass while the percentage was 0.28 % (95 %CI: 0.20−0.38) for DM. The distributions were 0.70 % (95 %CI: 0.57−0.85) versus 1.46 % (95 %CI: 1.27−1.67) for asymmetry and 0.24 % (95 %CI: 0.16−0.33) versus 0.54 % (95 %CI: 0.43−0.68) for obscured mass, among women screened with DBT versus DM, respectively. Spiculated mass was the most common feature among women diagnosed with non-luminal A-like cancer after DBT and after DM. Conclusions Spiculated mass was the dominant feature for breast cancer among women screened with DBT while calcifications was the most frequent feature for DM. Further studies exploring the clinical relevance of mammographic features visible particularly on DBT are warranted.publishedVersio

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 nationwide 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

Experience of pain during mammographic screening by three different compression paddles

Introduction - Experience of pain during screening mammography is shown to affect further attendance negatively. We aimed to explore the experience of pain during screening mammography using three different breast compression paddles. Methods - Using a self-report questionnaire, we collected information on pain experienced during mammography from 938 women screened in Bodø at Nordland Hospital County in 2018, as a part of BreastScreen Norway. Pain was assessed by a numeric rating scale (NRS, 0–10). A fixed paddle, a flexible paddle or a fixed paddle standardizing pressure (study paddle) were used during screening. Compression force (kg) was recorded by the radiographers for each screening examination. Log-binomial regression was used to determine the relative risk (RR) of severe (≥7 on NRS) versus mild/moderate ( Results - Mean score of self-reported experienced pain was 2.8 for the fixed, 2.3 for the flexible and 2.8 for the study paddle (p Conclusion - Women screened with the flexible paddle reported lower experience of pain than those screened with the fixed or study paddle

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

Cost differences between digital tomosynthesis and standard digital mammography in a breast cancer screening programme: results from the To-Be trial in Norway

Background Several studies in Europe and the US have shown promising results favouring digital breast tomosynthesis compared to standard digital mammography (DM). However, the costs of implementing the technology in screening programmes are not yet known. Methods A randomised controlled trial comparing the results from digital breast tomosynthesis including synthetic mammograms (DBT) vs. DM was performed in Bergen during 2016 and 2017 as a part of BreastScreen Norway. The trial included 29,453 women and allowed for a detailed comparison of procedure use and screening, recall and treatment costs estimated at the individual level. Results The increased cost of equipment, examination and reading time with DBT vs. DM was €8.5 per screened woman (95% CI 8.4−8.6). Costs of DBT remained significantly higher after adding recall assessment costs, €6.2 (95% CI 4.6−7.9). Substantial reductions in either examination and reading times, price of DBT equipment or price of IT storage and connectivity did not change the conclusion. Adding treatment costs resulted in too wide confidence intervals to draw definitive conclusions (additional costs of tomosynthesis €9.8, 95% CI –56 to 74). Performing biopsy at recall, radiation therapy and chemotherapy was significantly more frequent among women screened with DBT. Conclusion The results showed lower incremental costs of DBT vs. DM, compared to what is found in previous cost analyses of DBT and DM. However, the incremental costs were still higher for DBT compared with DM after including recall costs. Further studies with long-term treatment data are needed to understand the complete costs of implementing DBT in screening

Standardised or individualised X-ray tube angle for mediolateral oblique projection in digital mammography?

Introduction - We aimed to investigate whether there were any differences in positioning criteria related to the presentation of the pectoralis major muscle (pectoral muscle) for women of different heights using a standardized 60° X-ray tube angle for mammograms in mediolateral oblique (MLO) projection. Methods - Data from MLO mammograms of right breasts of 45,193 women screened in BreastScreen Norway 2016–2019 were used. The positioning criteria were related to the pectoral muscle length (measure A and measure B), width and shape and considered adequate or inadequate depending on the degree of fulfilling the criteria. Data associated with the pectoral muscle were extracted from Volpara, an automated software for breast density assessment. Information on height was obtained from a self-reported questionnaire received by the women together with the invitation to attend the screening program. Women were divided into three groups based on the height percentiles (P) in the Norwegian growth curves: 75th percentile (>P75th: >170 cm). Logistic regression was used to analyse the odds of adequate pectoral muscle length A and B, and shape, adjusting each model for screening technique and equipment model. Results were presented with odds ratios (OR) and 95% confidence intervals (CI). Results - Mean age of the screened women was 61.5 (SD = 4.8) years. The adequate measure for the pectoral muscle length A was obtained for 25.9% (11,724/45,193), length B for 76.3% (34,489/45,193), width for 75.0% (33,894/45,193) and shape for 97.6% (44,118/45,193) of the mammograms. Adjusted odds of an adequate pectoral muscle length A were lower for women of P75th (OR = 1.08, 95% CI 1.02–1.14) compared to women of P25-75. Odds of an adequate pectoral muscle shape were higher for women of P75th (OR = 0.92, 95% CI 0.87–0.97) compared to women of P25-75th. Conclusion - The 60° X-ray tube angle might suit most of the female population offered mammographic screening in Norway, but women of a relatively low height (163 cm or lower) might benefit from an X-ray tube angle less than 60-degrees