Den offentlige mammografiscreeningen i Norge Resultater fra programmet og relaterte forskningsprosjekter Solveig Hofvind, PhD Kreftregisteret, Oslo, Norge Odense, 28. januar 2011
Hendelse per 100,000 kvinne Aldersjusterte rater* av forekomst og død av brystkreft i Norge, 1956-2008 (*justert etter populasjonen av kvinner bosatt i Norge i januar 1981) 120 100 80 60 40 20 0 År
1956 1960 1964 1968 1972 1976 1980 1984 1988 1992 1996 2000 2004 2008 Forekomst per 100 000 kvinner Aldersspesifikk forekomst av infiltrerende brystkreft i Norge, 1956-2008 (aldersjustert for 1981 populasjonen) 400 350 25-39 år 40-49 år 50-59 år 60-69 år 70+ år 300 250 200 150 100 50 0 Diagnoseår
Rate per 100.000 kvinneår Forekomst av brystkreft før og etter oppstart av organisert mammografiscreening, 1990-94 og 2004-08 350 1990-94 2004-08 300 250 200 150 100 50 0 0-4 10-14 20-24 30-34 40-49 55-59 65-69 75-79 85-89 Aldersgrupper (år) 4
Forventet forekomst av brystkreft med og uten screening - jfr Boer R et al, Lancet,1994 Boer R et al, Lancet, 1994
1987 HT og brystkreft 1989 1991 1993 1995 1997 1999 2001 2003 Rate per 100.000 kvinneår 2005 2007 2009 Salg av kombinasjonspreparater med østrogen og progesteron (ATC gruppe G03F) 1987-2009 i forhold til formuleringer, gitt i antall DDDs/dag (DDD=1 tablett for alle preparatene) Andre Faste lavdosekombinasjonaer av estradiol (1 mg) og norethisterone (0.5 mg) Faste kombinasjoner av estradiol (2 mg) and norethisterone (1 mg) Sekvensielle kombinasjoner av estradiol and levonorgestrel Sekvensielle kombinasjoner av estradiol og norethisterone 350 300 250? 45-49 50-69 200 150 100 50 0 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 Diagnoseår
Number of DDDs/day Salg av rene rene østrogenpreparater (A) og østrogen og progesteronpreparater (B) 1987-2009 i DDDs/dag 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 2007 2009 Number of DDDs/day 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 2007 2009 A B 140000 Other Estriol and other estrogens for vaginal application Estradiol patches (DDD=0.05mg) Estradiol tabl (DDD=2 mg) Tibolone (DDD=2.5 mg) 140000 Other Low dose fixed combinations, estradiol (1 mg) and norethisterone (0.5 mg) Fixed combinations, estradiol (2 mg) and norethisterone (1 mg) Sequential combinations, estradiol and levonorgestrel Sequential combinations, estradiol and norethisterone 120000 120000 100000 100000 80000 80000 60000 60000 40000 40000 20000 20000 0 0 Years Years
Frekvens % Tid fra diagnose til død av brystkreft blant kvinner 50-69 år, døde av brystkreft i 1991-95, Tid siden diagnose T. Haldorsen, The Cancer Registry, 2009
Antall (n) Antall kvinner 50-69 år, døde av brystkreft etter screeningstatus Invitert før diagnose Invitert etter diagnose Ikke invitert T. Haldorsen, The Cancer Registry, 2009
Rater per 100 000 Aldersjustert dødelighet av brystkreft i Norge, 1970-2007 Dødsår Kvinner 55-74 år Pilotfylkene Kvinner 55-74 år Alle andre fylker
0 0 20 40 60 80 Per 100.000 personår 20 40 60 80 100 120 100 120 Rogaland Hordaland Aldersjustert (w) dødelighet av brystkreft blant kvinner 55-74 år i Rogaland Aldersjustert (w) dødelighet av brystkreft blant kvinner 55-74 år i Hordaland 1970 1975 1980 1985 1990 1995 2000 2005 2010 År 1970 1975 1980 1985 1990 1995 2000 2005 2010 År
Mammografiprogrammet The Norwegian Breast Cancer Screening Program Ledes av Helse- og omsorgsdepartementet Administrert fra Kreftregisteret Samarbeid mellom: Kreftregisteret Folkehelseinstituttet Statens strålevern Helseforetakene/fylkene
Side 18: Hovedmålet for Mammografiprogrammet er å oppnå 30% reduksjon i dødelighet av brystkreft for kvinner som inviteres til screening.
Mammografiprogrammet Stasjonære og mobile enheter Two views hvert annet år Uavhengig dobbelttyding Recalls ved BDS All aktivitet rapportert til Kreftregisteret Kvalitetsmanual Rådgivingsgruppe Invitasjoner: Målgruppe: Egenkostnader: Personlig brev, 11-sifret personnummer En påminnelse 520,000 kvinner, 50-69 år 25 Euro/35 US$
Recalls and detection rates, 1996-2005
Recall rater og biopsier
Brystkreft blant etterinnkalte (PPV-1) og deteksjonsrate
Tumorkarakteristikk infiltrerende brystkreft - 1980-2007 - Kvinner 50-69 år - Akershus, Hordaland, Oslo and Rogaland - 1984-1995: Før oppstart av Mammografiprogrammet - 1996-2007: Etter oppstart av Mammografiprogrammet
Histologisk morfologi Før Mp Etter Mp 1984-1995 1996-2007 Ikke screening Utenfor Mp Screening detektert n = 3635 n = 3235 n = 3634 Invasive Ductal Cancer 85.3%* 79.3%* 81.5 % Invasive Lobular Cancer 8.0%* 12.3%* 10.4 % Mucinous Cancer 1.7% 1.6% 2.0 % Tubular Cancer 1.0%* 1.8%* 3.5 % Pagets disease 2.1%* 1.3%* 0.4 % Andre invasive cancers 1.8% 3.7%* 2.2 % * Chi square test, p-value <0.05 når sammenlignet med screening detekterte tilfeller
Stadium Før Mp Etter Mp 1984-1995 1996-2007 Ikke screening Utenfor Mp Screening detektert n = 3635 n = 3235 n = 3634 Stadium I 50.4 %* 48.8%* 70.4 % Stadium II 38.8 %* 42.9%* 28.3 % Stadium III 4.5 %* 2.8%* 0.8 % Stadium IV 6.3 %* 5.5%* 0.5 % Missing informasjon (n) 43 39 8 * Chi square test, p-value <0.05 når sammenlignet med screening detekterte tilfeller
Tumorstørrelse Før Mp Etter Mp 1984-1995 1996-2007 Ikke screening Utenfor Mp Screening detektert n = 3635 n = 3235 n = 3634 20 mm 55.8 %* 61.1%* 82.9 % >20 cm - 50 mm 33.5 %* 31.5%* 15.4 % > 50mm 10.7 %* 7.5%* 1.7 % Missing informasjon (n) 1923 739 433 * Chi square test, p-value <0.05 når sammenlignet med screening detekterte tilfeller
Metastaser Før Mp Etter Mp 1984-1995 1996-2007 Ikke screening Utenfor Mp Screening detektert N = 3635 N = 3235 N = 3634 Lymfeknuter Positive 38.7 %* 42.3%* 25.6 % Negative 61.3 %* 57.7%* 74.4 % Missing informasjon (n) 702 437 269 Fjernmetastaser metastaser Ja 6.7 %* 7.9%* 0.6 % Nei 93.3 %* 92.1%* 99.4 % Missing informasjon (n) 797 1071 889 * Chi square test, p-value <0.05 når sammenlignet med screening detekterte tilfeller
Kirurgi Før Mp Etter Mp 1984-1995 1996-2007 Ikke screening Utenfor Mp Screening detektert n = 3635 n= 3235 n = 3634 Breast Conservative 13.3%* 39.0%* 57.1% Mastectomy 86.7%* 61.0%* 42.9% Missing informasjon (n) 670 210 39 * Chi square test, p-value <0.05 når sammenlignet med screening detekterte tilfeller
Tumor karakteristikk Screening og intervallkreft Screening Intervall (n=5,978) (n=1,279) Morfologi DCIS (%) 17.4 8.3 IDC (%) 70.7 72.9 ILC (%) 7.9 13.0 Andre (%) 3.9 5.8 Tumorstørrelse Mean (mm) 14.7 21.2 Median (mm) 13 18 Metastaser (%) 25.4 44.3 Grad I (%) 36.2 20.7 II (%) 48.2 48.6 III (%) 15.6 30.6
Fordeling av grad (stolper) Fordeling av lympfeknutespredning (prikket linje) Fordeling av grad (stolper) Fordeling av lympfeknutespredning (prikket linje) Prognostisk tumorkarakteristikk screening og intervallkreft 100 % 80 % 60 % 11 13 38 Grade 1 Grade 2 Grade 3 50 19 57 26 26 100 % 80 % 60 % 13 43 Grade 1 Grade 2 Grade 3 22 46 28 38 48 40 % 20 % 0 % 52 <=10mm 36.4% 37 11-15mm 30.4% 24 16-20mm 16.1% 56 57 18 17 21-30mm 12.2% >30mm 4.8% 40 % 20 % 0 % 45 <=10mm 22.1% 32 11-15mm 25.5% 54 18 16-20mm 23.4% 53 21-30mm 3.1% 44 9 8 >30mm 25.9% Tumorgrupper (i mm) og fordeling av gruppene (%) Tumorgrupper (i mm) og fordeling av gruppene (%) Infiltrerende screeningdetektert brystkreft (n 4,500) Infiltrerende intervallkreft (n 1,050)
Andel intervallkreft diagnostisert (%) Proportion of interval cancers diagnosed Intervallkreft 40 35 30 Other invasive breast cancers Invasive Lobular Carcinoma Invasive Ductal Carcinoma Ductal Carcinoma in Situ 25 20 15 10 5 0 1-6 7-12 13-18 19+ Months after screening Måneder etter screening
doi: 10.1148/radiol.2372041174 November 2005 Radiology, 237, 437-443.
Study design, review of interval cancers
Missed interval cancers by review design 231 interval cancers Design Number and proportion of missed cancers n % 95% CI Mixed blind individual 46 19.9 (15.0-25.7) Mixed blind pairs 54 23.4 (18.1-29.4) Informed individual 83 35.9 (29.7-42.5) Informed consensus 78 33.8 (27.7-40.3)
Conclusion The proportion of interval cancers classified as missed varied from 1.3% to 35.5% according to review design
Missed screen-detected and interval cancers in analogue and digital mammography screening in Norway Solveig Hofvind, Cancer Registry of Norway Anne L Abrahamsen, The Hospital in Vestfold, Norway Solveig Roth Hoff, Aalesund Hospital, Norway
Aim of the study What is the percentage of missed screen-detected and interval cancers in screen film (SFM) versus full field digital (FFDM) mammography screening? Which mammographic features are characteristic for missed cases in SFM versus FFDM?
Material Møre and Romsdal 2002 analogue (SFM) Vestfold 2004 digital (FFDM)
Material Møre and Romsdal 2002 analogue (SFM) Vestfold 2004 digital (FFDM) SFM FFDM Screen-detected cancers 123 86 Interval cancers 81 49
The review Consensus by four breast imaging specialists Index screening mammograms Diagnostic mammograms Pathologic reports Classification Missed Minimal sign actionable Minimal sign not actionable True Occult Missed Missed True True True
Screen-detected cancers SFM (n=123) FFDM (n=86) Missed 12% 11% Minimal sign actionable 9% 9% Minimal sign not actionable 37% 34% True 42% 47% Interval cancer SFM (n=81) FFDM (n=49) Missed 22% 20% Minimal sign actionable 7% 12% Minimal sign not actionable 32% 27% True 38% 41%
Mammographic tumor size in missed cases Screen-detected SFM FFDM Index mammography (mean) 12.4mm 9.4mm Diagnostic mammography (mean) 17.1mm 14.2mm Index mammography (median) 11mm 9mm Diagnostic mammography (median) 18mm 15.5mm Interval cancers SFM FFDM Index mammography (mean) 15.0mm 11.9mm Diagnostic mammography (mean) 19.6mm 17.6mm Index mammography (median) 15.5mm 12mm Diagnostic mammography (median) 20.5mm 18mm
Conclusions Between 20 and 30% of the interval and screen detected cancers detected are missed at previous screening exam Mass and calcifications are the most common mammographic features in missed cases The results are of considerable interest for further understanding of tumor growth
Aim: To compare the proportions and radiological features of discordant and concordant screendetected cancers in a population-based nationwide mammography screening program
Independent Double Reading with Consensus in the NBCSP 1; Negative 1 + 1 Negative 2; Probably benign 3; Indeterminate 4; Probably malignant 5; Malignant 2+ by one or both radiologists Discussed at a consensus meeting Recall/no recall
The Radiologists Inclusion criteria for this study: Reading >500 screening mammograms in 1 year: 123 radiologists 107 radiologists Annual average: 3,919 (range 525-13,395) Total average: 19,745 (range 525-107,161) 80% read >2000 annually 35% read >5000 annually
Study population Screens: n=1.083.870 Screen-detected cancers: n=5.611 Independent double reading Negative n=957.495 (92.6%) Discordant n=54.447 (5.3%) Concordant n=21.928 (2.1%) Consensus meeting Consensus meeting Dismissed n=36.380 3.5% (screens) 66.8%(discordants) Recall n=18.067 1.8% (screens) 33.2% (discordants) Dismissed n=3.932 0.4% (screens) 17.9%(concordants) Recall n=17.996 1.7% (screens) 82.1% (concordants) Breast cancer n=1.326 (23.6%) Breast cancer n=4.285 (76.4%) Interval cancer n=1.674 (0.17%) Interval cancer n=105 (0.29%) Interval cancer n=12 (0.31%)
Inter-reader Variability Reader B Reader A Score 1 Score 2 Score 3 Score 4 Score 5 Overall numbers of scores Score 1 n=0 0% n=639 11.4% n=526 9.4% n=126 2.2% n=35 0.6% N=1,326 23.6% Score 2 n=527 9.4% n=701 12.5% n=117 2.1% n=30 0.5% N=1,375 24.5% Score 3 n=836 14.9% n=586 10.4% n=98 1.7% N=1,520 27.1% Score 4 n=446 7.9% n=434 7.7% N=880 15.7% Score 5 n=510 9.1% Overall numbers of scores N=510 9.1% N=5,611 100%
Mammographic Features Mammographic features Discordant (n=1,331) Concordant (n=4,280) p-value Mass Spiculated* 27.7% 30.8% 0.048 Circumscribed 2.8% 2.4% 0.439 Poorly defined mass or asymmetric density 33.2% 33.8% 0.712 Calcifications Calcifications only 23.6% 17.1% <0.001 Mass with calcifications 11.1% 15.4% <0.001 Other features 0.7% 0.5% 0.616 Missing / information not available N=102 N=321 * Including distortion
Histopathological Types Discordant (No=1,331) Concordant (No=4,280) All cancers (No=5,611) DCIS 24% 16% 18% Invasive DC 63% 73%* 71% Invasive LC 9% 7%* 8% Other invasive 4% 4% 4% * Statistically significant different from discordant cancers (p<0.05)
Conclusions: 24% of the screen-detected cancers in a nationwide, population-based mammography screening program are interpreted ( overlooked ) as negative by one of two independent readers Spiculated and poorly defined masses, distortion and asymmetric density contributes to the majority of the discordant cancers Calcifications with or without an associated mass seem to represent a challenging mammographic feature in the initial interpretation of screening mammograms
Missed and true interval (n=81) and screen-detected (n=123) cancers Interval cancer (N=81) Screen-detected cancer * (N=123) All (N=204) % % % Missed 22.2 12.2 16.2 Minimal signs actionable 7.4 8.9 8.3 Minimal signs not actionable 32.1 37.4 35.3 True 38.3 41.5 40.2 * Screen-detected cancer in subsequently screened women in the organized screening program
Mammographic features in discordant and concordant cases Discordant cancer (n=30) Concordant cancer (n=93) Chi square Mass 53.3% 73.1% 0.072 Calcifications 30.0% 18.3% 0.267 Architectural distortion 13.3% 4.3% 0.187 Asymmetry 3.3% 1.1% 0.984 Occult - 3.2% 0.753
Calcifications in DCIS by grade Accepted for publication in Acta Radiologica, January 2011 Hofvind S, Iversen BF, Eriksen L, Styr B, Kjellevold K, Kurtz KD
Van Neuys grade distribution Rogaland 1995-2007, n=213 Age-groups (years at diagnosis) 50-69 50-54 55-59 60-64 65-69 Test for trend 1 Grade 1 17.1% 21.3% 9.4% 22.5% 15.8% 0.742 Grade 2 10.6% 14.7% 4.7% 10.0% 13.2% 0.786 Grade 3 72.4% 64.0% 85.9% 67.5% 71.1% 0.643 1 Chi square test for trend
Morphology of calcifications Calcification morphology by grade in 202 screen-detected DCIS Non-high grade (n, %) High grade (n, %) Total (n, %) p-value 2 Fine pleomorphic (n, %) 24 (31%) 53 (69%) 77 (100%) 0.278 Fine linear and 10 (16%) 52 (84%) 62 (100%) 0.045 fine linear branching (n, %) Amorphous (n, %) 17 (31%) 38 (69%) 55 (100%) 0.457 Coarse heterogeneous (n, %) 1 (17%) 5 (83%) 6 (100%) --- Punctated (n, %) 1 (50%) 1 (50%) 2 (100%) --- Total (n, %) 53 (26%) 149 (74%) 202 (100%) < 0.001 p-value (Chi-square test) between non-high (Van Nuys nuclear grade 1 and 2) and high-grade (Van Nuys nuclear grade 3) lesions
Morphology of calcifications Calcification morphology by grade in 202 screen-detected DCIS Non-high grade (n, %) Fine pleomorphic (n, %) 24 (31%) (45%) Fine linear and 10 (16%) fine linear branching (n, %) (19%) Amorphous (n, %) 17 (31%) (32%) Coarse heterogeneous (n, %) 1 (17%) (2%) Punctated (n, %) 1 (50%) (2%) Total (n, %) 53 (26%) (100%) High grade (n, %) 53 (69%) (36%) 52 (84%) (35%) 38 (69%) (26%) 5 (83%) (3%) 1 (50%) (< 1%) 149 (74%) (100%) Total (n, %) 77 (100%) (38%) 62 (100%) (31%) 55 (100%) (27%) 6 (100%) (3%) 2 (100%) (1%) 202 (100%) (100%) p-value 2 0.278 0.045 0.457 --- --- < 0.001 p-value (Chi-square test) between non-high (Van Nuys nuclear grade 1 and 2) and high-grade (Van Nuys nuclear grade 3) lesions
Morphology of calcifications Morphology of calcifications DCIS: distribution and morphology of calcifications by grade Distribution of calcifications Non-high grade 1 Grouped Segmental Regional Linear Diffuse Total Fine pleomorphic 18% 13% 9% 2% 2% 45% Fine linear /Fl branching 13% 6% -- -- 19% Amorphous 17% 8% 8% -- -- 32% Coarse heterogeneous 2% -- -- -- -- 3% Punctated 2% -- -- -- -- 3% Total 28 (53%) 11 (21%) 12 (23%) 1 (2%) 1 (2%) 53 (100%) High grade 2 Fine pleomorphic 20% 7% 6% 3% -- 36% Fine linear/fl branching 11% 14% 5% 5% -- 35% Amorphous 18% 2% 5% -- -- 26% Coarse heterogeneous 2% -- -- 1% -- 3% Punctated -- -- 1%) -- 1% Total 76 (51%) 33 (23%) 26 (17%) 14 (9%) -- 149 (100%) 1 Non-high grade lesion (Van Nuys nuclear grade 1 and 2) 2 High grade lesion (Van Nuys nuclear grade 3)
Radiological Sensitivity and Specificity in opportunistic and organized screening for early detection of breast cancer
Radiological Sensitivity and Specificity Initial assessment: Negative = Not recallet Positive = Recalled Final assessment: Negative= No recomendation for biopsy Positive= Biopsy recommended
Initial assessment Vermont, USA and Norway women 50-69 years old All screening intervals, 1 year follow up Not age adjusted Vermont 141,284 screens Norway 360,872 screens True Negative 90.1% 97.2% False Positive 9.4% 2.2% True Positive 0.43% 0.51% False Negative 0.08% 0.05%
Sensitivity and Specificity age adjusted analysis Vermont 1 year interval 1 year follow-up Norway 2 year screen 2 year follow-up Initial assess 82.0% / 90.8% 75.7% /97.8% Final assess 73.6% / 98.9% 74.4% / 99.5%
Sensitivity and Specificity What does this information add? The sensitivity decreased from initial to final assessment in VT, not in Norway Specificity almost stable in initial and final assessment, both in VT and NO
Oppsummering / konklusjon Mammografiscreening: Mange aspekter mange spørsmål mange fasiter Delmål (deteksjon, tumorkarakteristikk etc) Dødelighet Hvem skal stille spørsmålene? Hvem skal lage fasitene?
Organisert mammografiscreening Erfaringer / læring / kunnskapsutvikling opprettelse av BDS tidligdiagnostikk tidsaspekter organisering og drift Q of life Screening er et eget fag / disiplin; ledelse, medisin, og epidemiologi