Den offentlige mammografiscreeningen i Norge

Transkript

1 Den offentlige mammografiscreeningen i Norge Resultater fra programmet og relaterte forskningsprosjekter Solveig Hofvind, PhD Kreftregisteret, Oslo, Norge Odense, 28. januar 2011

2 Hendelse per 100,000 kvinne Aldersjusterte rater* av forekomst og død av brystkreft i Norge, (*justert etter populasjonen av kvinner bosatt i Norge i januar 1981) År

3 Forekomst per kvinner Aldersspesifikk forekomst av infiltrerende brystkreft i Norge, (aldersjustert for 1981 populasjonen) år år år år 70+ år Diagnoseår

4 Rate per kvinneår Forekomst av brystkreft før og etter oppstart av organisert mammografiscreening, og Aldersgrupper (år) 4

5 Forventet forekomst av brystkreft med og uten screening - jfr Boer R et al, Lancet,1994 Boer R et al, Lancet, 1994

6

7 1987 HT og brystkreft Rate per kvinneår Salg av kombinasjonspreparater med østrogen og progesteron (ATC gruppe G03F) 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 ? Diagnoseår

8 Number of DDDs/day Salg av rene rene østrogenpreparater (A) og østrogen og progesteronpreparater (B) i DDDs/dag Number of DDDs/day A B Other Estriol and other estrogens for vaginal application Estradiol patches (DDD=0.05mg) Estradiol tabl (DDD=2 mg) Tibolone (DDD=2.5 mg) 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 Years Years

9

10 Frekvens % Tid fra diagnose til død av brystkreft blant kvinner år, døde av brystkreft i , Tid siden diagnose T. Haldorsen, The Cancer Registry, 2009

11 Antall (n) Antall kvinner år, døde av brystkreft etter screeningstatus Invitert før diagnose Invitert etter diagnose Ikke invitert T. Haldorsen, The Cancer Registry, 2009

12 Rater per Aldersjustert dødelighet av brystkreft i Norge, Dødsår Kvinner år Pilotfylkene Kvinner år Alle andre fylker

13 Per personår Rogaland Hordaland Aldersjustert (w) dødelighet av brystkreft blant kvinner år i Rogaland Aldersjustert (w) dødelighet av brystkreft blant kvinner år i Hordaland År År

14

15 Mammografiprogrammet The Norwegian Breast Cancer Screening Program Ledes av Helse- og omsorgsdepartementet Administrert fra Kreftregisteret Samarbeid mellom: Kreftregisteret Folkehelseinstituttet Statens strålevern Helseforetakene/fylkene

16 Side 18: Hovedmålet for Mammografiprogrammet er å oppnå 30% reduksjon i dødelighet av brystkreft for kvinner som inviteres til screening.

17 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, år 25 Euro/35 US$

18

19 Recalls and detection rates,

20 Recall rater og biopsier

21 Brystkreft blant etterinnkalte (PPV-1) og deteksjonsrate

22 Tumorkarakteristikk infiltrerende brystkreft Kvinner år - Akershus, Hordaland, Oslo and Rogaland : Før oppstart av Mammografiprogrammet : Etter oppstart av Mammografiprogrammet

23 Histologisk morfologi Før Mp Etter Mp 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

24 Stadium Før Mp Etter Mp 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) * Chi square test, p-value <0.05 når sammenlignet med screening detekterte tilfeller

25 Tumorstørrelse Før Mp Etter Mp Ikke screening Utenfor Mp Screening detektert n = 3635 n = 3235 n = 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) * Chi square test, p-value <0.05 når sammenlignet med screening detekterte tilfeller

26 Metastaser Før Mp Etter Mp 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) Fjernmetastaser metastaser Ja 6.7 %* 7.9%* 0.6 % Nei 93.3 %* 92.1%* 99.4 % Missing informasjon (n) * Chi square test, p-value <0.05 når sammenlignet med screening detekterte tilfeller

27 Kirurgi Før Mp Etter Mp 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) * Chi square test, p-value <0.05 når sammenlignet med screening detekterte tilfeller

28 Tumor karakteristikk Screening og intervallkreft Screening Intervall (n=5,978) (n=1,279) Morfologi DCIS (%) IDC (%) ILC (%) Andre (%) Tumorstørrelse Mean (mm) Median (mm) Metastaser (%) Grad I (%) II (%) III (%)

29 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 % Grade 1 Grade 2 Grade % 80 % 60 % Grade 1 Grade 2 Grade % 20 % 0 % 52 <=10mm 36.4% mm 30.4% mm 16.1% mm 12.2% >30mm 4.8% 40 % 20 % 0 % 45 <=10mm 22.1% mm 25.5% mm 23.4% mm 3.1% >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)

30 Andel intervallkreft diagnostisert (%) Proportion of interval cancers diagnosed Intervallkreft Other invasive breast cancers Invasive Lobular Carcinoma Invasive Ductal Carcinoma Ductal Carcinoma in Situ Months after screening Måneder etter screening

31 doi: /radiol November 2005 Radiology, 237,

32 Study design, review of interval cancers

33 Missed interval cancers by review design 231 interval cancers Design Number and proportion of missed cancers n % 95% CI Mixed blind individual ( ) Mixed blind pairs ( ) Informed individual ( ) Informed consensus ( )

34 Conclusion The proportion of interval cancers classified as missed varied from 1.3% to 35.5% according to review design

35 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

36 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?

37 Material Møre and Romsdal 2002 analogue (SFM) Vestfold 2004 digital (FFDM)

38 Material Møre and Romsdal 2002 analogue (SFM) Vestfold 2004 digital (FFDM) SFM FFDM Screen-detected cancers Interval cancers 81 49

39 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

40 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%

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

42 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

43

44 Aim: To compare the proportions and radiological features of discordant and concordant screendetected cancers in a population-based nationwide mammography screening program

45 Independent Double Reading with Consensus in the NBCSP 1; Negative 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

46 The Radiologists Inclusion criteria for this study: Reading >500 screening mammograms in 1 year: 123 radiologists 107 radiologists Annual average: 3,919 (range ,395) Total average: 19,745 (range ,161) 80% read >2000 annually 35% read >5000 annually

47 Study population Screens: n= Screen-detected cancers: n=5.611 Independent double reading Negative n= (92.6%) Discordant n= (5.3%) Concordant n= (2.1%) Consensus meeting Consensus meeting Dismissed n= % (screens) 66.8%(discordants) Recall n= % (screens) 33.2% (discordants) Dismissed n= % (screens) 17.9%(concordants) Recall n= % (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%)

48 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= % n= % n= % n=35 0.6% N=1, % Score 2 n= % n= % n= % n=30 0.5% N=1, % Score 3 n= % n= % n=98 1.7% N=1, % Score 4 n= % n= % N= % Score 5 n= % Overall numbers of scores N= % N=5, %

49 Mammographic Features Mammographic features Discordant (n=1,331) Concordant (n=4,280) p-value Mass Spiculated* 27.7% 30.8% Circumscribed 2.8% 2.4% Poorly defined mass or asymmetric density 33.2% 33.8% Calcifications Calcifications only 23.6% 17.1% <0.001 Mass with calcifications 11.1% 15.4% <0.001 Other features 0.7% 0.5% Missing / information not available N=102 N=321 * Including distortion

50 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)

51 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

52

53 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 Minimal signs actionable Minimal signs not actionable True * Screen-detected cancer in subsequently screened women in the organized screening program

54 Mammographic features in discordant and concordant cases Discordant cancer (n=30) Concordant cancer (n=93) Chi square Mass 53.3% 73.1% Calcifications 30.0% 18.3% Architectural distortion 13.3% 4.3% Asymmetry 3.3% 1.1% Occult - 3.2% 0.753

55 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

56 Van Neuys grade distribution Rogaland , n=213 Age-groups (years at diagnosis) Test for trend 1 Grade % 21.3% 9.4% 22.5% 15.8% Grade % 14.7% 4.7% 10.0% 13.2% Grade % 64.0% 85.9% 67.5% 71.1% Chi square test for trend

57 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%) Fine linear and 10 (16%) 52 (84%) 62 (100%) fine linear branching (n, %) Amorphous (n, %) 17 (31%) 38 (69%) 55 (100%) 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%) < p-value (Chi-square test) between non-high (Van Nuys nuclear grade 1 and 2) and high-grade (Van Nuys nuclear grade 3) lesions

58 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 < p-value (Chi-square test) between non-high (Van Nuys nuclear grade 1 and 2) and high-grade (Van Nuys nuclear grade 3) lesions

59 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% % Amorphous 17% 8% 8% % Coarse heterogeneous 2% % Punctated 2% % 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% % Coarse heterogeneous 2% % -- 3% Punctated %) -- 1% Total 76 (51%) 33 (23%) 26 (17%) 14 (9%) (100%) 1 Non-high grade lesion (Van Nuys nuclear grade 1 and 2) 2 High grade lesion (Van Nuys nuclear grade 3)

60 Radiological Sensitivity and Specificity in opportunistic and organized screening for early detection of breast cancer

61 Radiological Sensitivity and Specificity Initial assessment: Negative = Not recallet Positive = Recalled Final assessment: Negative= No recomendation for biopsy Positive= Biopsy recommended

62 Initial assessment Vermont, USA and Norway women 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%

63 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%

64 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

65 Oppsummering / konklusjon Mammografiscreening: Mange aspekter mange spørsmål mange fasiter Delmål (deteksjon, tumorkarakteristikk etc) Dødelighet Hvem skal stille spørsmålene? Hvem skal lage fasitene?

66 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