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

Digital Breast Tomosynthesis : - the future screening tool for breast cancer?

Bakgrunn: Brystkreft er den vanligste kreftformen blant kvinner og en av de hyppigste årsakene til kreftdødsfall i Norge og globalt. Målsettingen med mammografiscreening er å oppdage brystkreft i et tidlig stadium og redusere dødeligheten av sykdommen. Studier har vist høyere deteksjon av screeningoppdagede krefttilfeller med digital brysttomosyntese som inkluderer ~200-250 bilder sammenlignet med standard digital mammografi (DM) med fire bilder. Vi utførte en randomisert kontrollert studie (RCT), Tomosyntese-studien i Bergen (To-Be1). Målsettingen med studien var å sammenligne tidligindikatorer i screening ved bruk av digital brysttomosyntese i kombinasjon med syntetiske 2D-bilder (DBT) versus standard DM. Avhandlingen inkluderer tre studier med følgende mål: Studie 1: Å sammenligne lesetid, stråledose, konsensus og tilbakekalling ved bruk av DBT og DM etter det første året av To-Be1. Studie 2: Å sammenligne tilbakekalling, falske positive screeningsresultater og screeningoppdaget kreft for kvinner med ulik mammografisk tetthet målt automatisk (Volpara tetthetsgrad, VDG 1-4) og med ulike screeningteknikker (DBT versus DM). Studie 3: Å undersøke fordeling av mammografiske funn hos kvinner tilbakekalt etter screening med DBT versus DM og analysere sammenhenger mellom mammografiske funn og det endelige resultatet av screeningundersøkelsen. Metode: Alle kvinner som deltok i screening utført i Bergen i løpet av 2016-2017 som en del av Mammografiprogrammet (n=32 976) ble invitert til å delta i To-Be1. Totalt aksepterte 89,3 % av kvinnene invitasjonen og ble randomisert til DBT eller DM. Etter uavhengig dobbelttyding med konsensus ble resultater etter DBT sammenlignet med DM. Mammografisk tetthet ble oppgitt som VDG 1-4, som er analog til kategoriene i BI-RADS´ 5. utgave. Radiologene klassifiserte mammografiske funn hos etterinnkalte kvinner etter en modifisert BI-RADS skala. Vi brukte deskriptive analyser og t-test for å sammenligne gjennomsnittsverdier, samt kji-kvadrat-test med tilhørende 95% konfidensintervall (KI) for å sammenligne kategorier. Log-binominale regresjonsmodeller ble brukt for å estimere relativ risiko. En p-verdi lavere enn 0,05 ble definert som statistisk signifikant. Vi brukte statistikkprogrammet STATA. Resultater: Studie 1: Gjennomsnittlig lesetid var 1:11 min:sek for DBT og 0:41 min:sek for DM i det første året av To-Be1. Det var ingen statistiske forskjeller i gjennomsnittlig stråledose for noen av tetthetskategoriene for DBT (2,96 mGy) versus DM (2,95 mGy). Tilbakekallingen var 3,0 % for DBT og 3,6 % for DM etter det første året med To-Be1. Studie 2: Etterundersøkelsesraten for kvinner med VDG 1 var 2,1% for DBT og 3,3% for DM, mens den var 3,2% for DBT og 4,3% for DM for de med VDG 2. Raten av falske positive screening resultater var 1,6% for DBT og 2,8% for DM for kvinner med VDG 1. For kvinner med VDG 2 var den 2,4% for DBT og 3,6 for DM. Ingen statistiske forskjeller i screeningoppdaget kreft ble funnet mellom DBT og DM for noen av tetthetskategoriene. Justert relativ risiko for tilbakekalling, falskt positivt screeningsresultat og screeningoppdaget kreft økte med VDG i DBT, mens det ikke ble funnet forskjeller i DM. Studie 3: Studien inkluderte 182 screeningdetekterte krefttilfeller (n=95 for DBT og n=87 for DM). Blant disse var 36,8% spikulerte masser for DBT mens det var 18,4% for DM. Kalk var det hyppigste mammografiske funnet for brystkrefttilfeller for de som var screenet med DM (23%). For DBT var andelen på 13,7%. Asymmetri, uskarp og skjult masse var mindre hyppig hos kvinner med et falsk positiv screening resultat etter screening med DBT versus DM. Konklusjon: Resultater fra To-Be1 indikerte at DBT var minst like god som DM når det gjelder etterundersøkelser og deteksjon av brystkreft, som betyr at DBT er trygt å bruke i screening. DBT var bedre egnet enn DM for kvinner med VDG 1 og 2 med hensyn til etterundersøkelsesrate og falske positive, mens deteksjon av brystkreft ikke var forskjellig. Det tok lengre tid å lese DBT enn DM bilder, og konsensus tok lengre tid med DBT. Mer kunnskap om forskjeller i mammografiske funn og sammenheng med screeningsresultater for DBT versus DM kan bidra til å ytterligere forbedre fordelene med DBT som et screeningverktøy.Background: Breast cancer is the most common cancer and one of the leading causes of cancer deaths in Norway and globally. Mammographic screening aims for early detection of breast cancer and reduced mortality from the disease. Studies have shown higher rates of screen-detected cancers for digital breast tomosynthesis including ~200-250 images compared to standard digital mammography (DM) including four images. We performed a randomized controlled trial (RCT), the Tomosynthesis trial in Bergen (To-Be1), were the aim was to compare early performance measures for digital breast tomosynthesis including synthesised 2D images (DBT) versus DM in screening. This thesis includes three studies with the following aims: Study 1: To compare preliminary results of reading time, radiation dose, consensus and recall for DBT and DM after the first year of To-Be1. Study 2: To compare recall, false positive screening results and screen-detected cancers by automated mammographic density (Volpara density grade, VDG 1-4) and screening technique (DBT versus DM). Study 3: To investigate distribution of mammographic features in women recalled after screening with DBT versus DM and assess associations between mammographic features and final outcome of the screening examination. Method: All women who attended the screening unit in Bergen during 2016-2017 as part of BreastScreen Norway (n=32 976) were invited to participate in To-Be1. In total, 89.3% of the women accepted the invitation and were randomized to undergo either DBT or DM. After independent double reading with consensus, results for DBT were compared with DM. Mammographic density were described by VDG 1-4 which are analogue to the categories in the BI-RADS 5th edition. The radiologists classified the mammographic features of recalled women according to a modified BI-RADS scale. We presented descriptive results and used t-tests to test for means, and chi-squared tests for categories with corresponding 95% confidence intervals (CI). Log-binominal regression models were used to estimate relative risks. A p-value lower than 0.05 was defined as statistically significant. We used STATA software. Results: Study 1: Mean reading time was 1:11 min:sec for DBT versus 0:41 min:sec for DM in the first year of To-Be1. Mean glandular dose did not differ statistically for women screened with DBT (2.96 mGy) versus DM (2.95 mGy). Recall was 3.0% for DBT and 3.6% for DM in the first year of To-Be1. Study 2: Recall rate for women with VDG 1 was 2.1% for DBT and 3.3% for DM, while it was 3.2% for DBT and 4.3% for DM for women with VDG 2. The rate of false positive screening results was 1.6% for DBT and 2.8% for DM for women with VDG 1. For women with VDG 2 it was 2.4% for DBT and 3.6% for DM. No statistical difference in screen-detected cancers was observed between DBT and DM in any density categories. Adjusted relative risk of recall, false positives and screen-detected cancers increased with VDG for DBT. No difference was found for DM. Study 3: The study included 182 screen detected cancers (n=95 DBT and n= 87 DM). 36.8% of those detected with DBT was spiculated mass, while it was 18.4 % for DM. Calcifications was the most frequent feature for breast cancer among those screened with DM (23.0%), which did not differ statistically from the 13.7% for DBT. Asymmetry, indistinct and obscured mass was less frequent in women with a false positive screening result after screening with DBT versus DM. Conclusion: Results from To-Be1 indicated DBT to be as least as good as DM in terms of recall and cancer detection, which means that DBT is safe for the women. DBT was superior to DM in women with VDG 1 and 2 (lower recall, fewer false positives, no difference in cancer detection). However, time spent on initial screen reading and on consensus was longer for DBT compared with DM. More knowledge of the differences in distribution of mammographic features and their association with screening outcome, might contribute to further improve the benefits of DBT as a screening tool for breast cancer.Doktorgradsavhandlin

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

Computer aided detection in mammography

Tese de mestrado integrado. Engenharia Electrotécnica e de Computadores. Faculdade de Engenharia. Universidade do Porto. 201

Caracterización de Patrones Anormales en Mamografías

Abstract. Computer-guided image interpretation is an extensive research area whose main purpose is to provide tools to support decision-making, for which a large number of automatic techniques have been proposed, such as, feature extraction, pattern recognition, image processing, machine learning, among others. In breast cancer, the results obtained at this area, they have led to the development of diagnostic support systems, which have even been approved by the FDA (Federal Drug Administration). However, the use of those systems is not widely extended in clinic scenarios, mainly because their performance is unstable and poorly reproducible. This is due to the high variability of the abnormal patterns associated with this neoplasia. This thesis addresses the main problem associated with the characterization and interpretation of breast masses and architectural distortion, mammographic findings directly related to the presence of breast cancer with higher variability in their form, size and location. This document introduces the design, implementation and evaluation of strategies to characterize abnormal patterns and to improve the mammographic interpretation during the diagnosis process. The herein proposed strategies allow to characterize visual patterns of these lesions and the relationship between them to infer their clinical significance according to BI-RADS (Breast Imaging Reporting and Data System), a radiologic tool used for mammographic evaluation and reporting. The obtained results outperform some obtained by methods reported in the literature both tasks classification and interpretation of masses and architectural distortion, respectively, demonstrating the effectiveness and versatility of the proposed strategies.Resumen. La interpretación de imágenes guiada por computador es una área extensa de investigación cuyo objetivo principal es proporcionar herramientas para el soporte a la toma de decisiones, para lo cual se han usado un gran número de técnicas de extracción de características, reconocimiento de patrones, procesamiento de imágenes, aprendizaje de máquina, entre otras. En el cáncer de mama, los resultados obtenidos en esta área han dado lugar al desarrollo de sistemas de apoyo al diagnóstico que han sido incluso aprobados por la FDA (Federal Drug Administration). Sin embargo, el uso de estos sistemas no es ampliamente extendido, debido principalmente, a que su desempeño resulta inestable y poco reproducible frente a la alta variabilidad de los patrones anormales asociados a esta neoplasia. Esta tesis trata el principal problema asociado a la caracterización y análisis de masas y distorsión de la arquitectura debido a que son hallazgos directamente relacionados con la presencia de cáncer y que usualmente presentan mayor variabilidad en su forma, tamaño y localización, lo que altera los resultados diagnósticos. Este documento introduce el diseño, implementación y evaluación de un conjunto de estrategias para caracterizar patrones anormales relacionados con este tipo de hallazgos para mejorar la interpretación y soportar el diagnóstico mediante la imagen mamaria. Los modelos aquí propuestos permiten caracterizar patrones visuales y la relación entre estos para inferir su significado clínico según el estándar BI-RADS (Breast Imaging Reporting and Data System) usado para la evaluación y reporte mamográfico. Los resultados obtenidos han demostrado mejorar a los resultados obtenidos por los métodos reportados en la literatura en tareas como clasificación e interpretación de masas y distorsión arquitectural, demostrando la efectividad y versatilidad de las estrategia propuestas.Doctorad

Digital breast tomosynthesis: A state of the art review

Digital Breast Tomosynthesis (DBT) is an X-ray mammography technique where multiple low-dose projection images of the breast are reconstructed in multiple tomographic images creating a semi-3D mammogram. This enables the visualization of a sequential set of thin sections of the breast, overcoming the masking effect of overlying fibroglandular breast tissue, then improving carcinoma detection and reducing false-positive cases. This review aims at describing current DBT technique, analyzing DBT in clinical practice and providing an overview of published studies on clinical experience with DBT in the screening and diagnostic settings