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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2020

Open Access 01-10-2020 | Breast Cancer | Epidemiology

Prognostic value of histopathological DCIS features in a large-scale international interrater reliability study

Authors: Emma J. Groen, Jan Hudecek, Lennart Mulder, Maartje van Seijen, Mathilde M. Almekinders, Stoyan Alexov, Anikó Kovács, Ales Ryska, Zsuzsanna Varga, Francisco-Javier Andreu Navarro, Simonetta Bianchi, Willem Vreuls, Eva Balslev, Max V. Boot, Janina Kulka, Ewa Chmielik, Ellis Barbé, Mathilda J. de Rooij, Winand Vos, Andrea Farkas, Natalja E. Leeuwis-Fedorovich, Peter Regitnig, Pieter J. Westenend, Loes F. S. Kooreman, Cecily Quinn, Giuseppe Floris, Gábor Cserni, Paul J. van Diest, Esther H. Lips, Michael Schaapveld, Jelle Wesseling, Grand Challenge PRECISION consortium

Published in: Breast Cancer Research and Treatment | Issue 3/2020

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Abstract

Purpose

For optimal management of ductal carcinoma in situ (DCIS), reproducible histopathological assessment is essential to distinguish low-risk from high-risk DCIS. Therefore, we analyzed interrater reliability of histopathological DCIS features and assessed their associations with subsequent ipsilateral invasive breast cancer (iIBC) risk.

Methods

Using a case-cohort design, reliability was assessed in a population-based, nationwide cohort of 2767 women with screen-detected DCIS diagnosed between 1993 and 2004, treated by breast-conserving surgery with/without radiotherapy (BCS ± RT) using Krippendorff’s alpha (KA) and Gwet’s AC2 (GAC2). Thirty-eight raters scored histopathological DCIS features including grade (2-tiered and 3-tiered), growth pattern, mitotic activity, periductal fibrosis, and lymphocytic infiltrate in 342 women. Using majority opinion-based scores for each feature, their association with subsequent iIBC risk was assessed using Cox regression.

Results

Interrater reliability of grade using various classifications was fair to moderate, and only substantial for grade 1 versus 2 + 3 when using GAC2 (0.78). Reliability for growth pattern (KA 0.44, GAC2 0.78), calcifications (KA 0.49, GAC2 0.70) and necrosis (KA 0.47, GAC2 0.70) was moderate using KA and substantial using GAC2; for (type of) periductal fibrosis and lymphocytic infiltrate fair to moderate estimates were found and for mitotic activity reliability was substantial using GAC2 (0.70). Only in patients treated with BCS-RT, high mitotic activity was associated with a higher iIBC risk in univariable analysis (Hazard Ratio (HR) 2.53, 95% Confidence Interval (95% CI) 1.05–6.11); grade 3 versus 1 + 2 (HR 2.64, 95% CI 1.35–5.14) and a cribriform/solid versus flat epithelial atypia/clinging/(micro)papillary growth pattern (HR 3.70, 95% CI 1.34–10.23) were independently associated with a higher iIBC risk.

Conclusions

Using majority opinion-based scores, DCIS grade, growth pattern, and mitotic activity are associated with iIBC risk in patients treated with BCS-RT, but interrater variability is substantial. Semi-quantitative grading, incorporating and separately evaluating nuclear pleomorphism, growth pattern, and mitotic activity, may improve the reliability and prognostic value of these features.
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Literature
1.
Virnig BA, Tuttle TM, Shamliyan T, Kane RL (2010) Ductal carcinoma in Situ of the breast: A systematic review of incidence, treatment, and outcomes. J Natl Cancer Inst. 102(3):170–178PubMed
2.
3.
4.
Ripping TM, Verbeek ALM, Fracheboud J, De Koning HJ, Van Ravesteyn NT, Broeders MJM (2015) Overdiagnosis by mammographic screening for breast cancer studied in birth cohorts in the Netherlands. Int J Cancer. 137(4):921–929PubMed
5.
Harding C, Pompei F, Burmistrov D, Welch HG, Abebe R, Wilson R (2015) Breast cancer screening, incidence, and mortality across US counties. JAMA Intern Med. 175(9):1483–1489PubMed
6.
van Luijt PA, Heijnsdijk EAM, Fracheboud J, Overbeek LIH, Broeders MJM, Wesseling J et al (2016) The distribution of ductal carcinoma in situ (DCIS) grade in 4232 women and its impact on overdiagnosis in breast cancer screening. Breast Cancer Res. 18(1):47PubMedPubMedCentral
7.
Erbas B, Provenzano E, Armes J, Gertig D (2006) The natural history of ductal carcinoma in situ of the breast: a review. Breast Cancer Res Treat 97(2):135–144PubMed
8.
Ryser MD, Weaver DL, Zhao F, Worni M, Grimm LJ, Gulati R et al (2019) Cancer outcomes in DCIS patients without locoregional treatment. J Natl Cancer Inst 111(9):952–960PubMedPubMedCentral
9.
Lari SA, Kuerer HM (2011) Biological markers in DCIS and risk of breast recurrence: a systematic review. J Cancer. 2:232PubMedPubMedCentral
10.
Visser LL, Groen EJ, Van Leeuwen FE, Lips EH, Schmidt MK, Wesseling J (2019) Predictors of an invasive breast cancer recurrence after DCIS: A Systematic Review and Meta-analyses. Cancer Epidemiol Biomark Prev 28(5):835–845
11.
Holland R, Peterse JL, Millis RR, Eusebi V, Faverly D, Van de Vijver MJ et al (1994) Ductal carcinoma in situ: a proposal for a new classification. Semin Diagn Pathol 11(3):167–180PubMed
12.
Pinder SE, Duggan C, Ellis IO, Cuzick J, Forbes JF, Bishop H et al (2010) A new pathological system for grading DCIS with improved prediction of local recurrence: Results from the UKCCCR/ANZ DCIS trial. Br J Cancer. 103(1):94–100PubMedPubMedCentral
13.
14.
Lagios MD (1990) Duct carcinoma in situ. Pathology and treatment. Surg Clin North Am. 70(4):873–883
15.
Silverstein MJ, Poller DN, Waisman JR, Colburn WJ, Barth A, Gierson ED et al (1995) Prognostic classification of breast ductal carcinoma-in-situ. Lancet 345(8958):1154–1157PubMed
16.
Sloane JP, Amendoeira I, Apostolikas N, Bellocq JP, Bianchi S, Boecker W et al (1998) Consistency achieved by 23 European pathologists in categorizing ductal carcinoma in situ of the breast using five classifications. European Commission Working Group on Breast Screening Pathology. Hum Pathol 29(10):1056–1062PubMed
17.
Wells WA, Carney PA, Eliassen MS, Grove MR, Tosteson ANA (2000) Pathologists’ agreement with experts and reproducibility of breast ductal carcinoma-in-situ classification schemes. Am J Surg Pathol 24(5):651–659PubMed
18.
Bethwaite P, Smith N, Delahunt B, Kenwright D (1998) Reproducibility of new classification schemes for the pathology of ductal carcinoma in situ of the breast. J Clin Pathol 51:450–454PubMedPubMedCentral
19.
Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ (2012) WHO classification of tumours of the breast, 4th edn. International Agency for Research on Cancer, Lyon
20.
21.
Poller DN, Silverstein MJ, Galea M, Locker AP, Elston CW, Blamey RW et al (1994) Ideas in pathology. Ductal carcinoma in situ of the breast: a proposal for a new simplified histological classification association between cellular proliferation and c-erbB-2 protein expression. Mod Pathol 7(2):257–262PubMed
22.
Elston CW, Sloane JP, Amendoeira I, Apostolikas N, Bellocq JP, Bianchi S et al (2000) Causes of inconsistency in diagnosing and classifying intraductal proliferations of the breast. Eur J Cancer 36(14):1769–1772PubMed
23.
Scott MA, Lagios MD, Axelsson K, Rogers LW, Anderson TJ, Page DL (1997) Ductal carcinoma in situ of the breast: Reproducibility of histological subtype analysis. Hum Pathol 28(8):967–973PubMed
24.
Schuh F, Biazús JV, Resetkova E, Benfica CZ, Edelweiss MIA (2010) Reproducibility of three classification systems of ductal carcinoma in situ of the breast using a web-based survey. Pathol Res Pract 206(10):705–711PubMed
25.
Schuh F, Biazús JV, Resetkova E, Benfica CZ, Ventura A, de Freitas Uchoa D et al (2015) Histopathological grading of breast ductal carcinoma in situ: validation of a web-based survey through intra-observer reproducibility analysis. Diagn Pathol 10(1):93PubMedPubMedCentral
26.
Elmore JG, Longton GM, Carney PA, Geller BM, Onega T, Tosteson ANA et al (2015) Diagnostic concordance among pathologists interpreting breast biopsy specimens. JAMA 313(11):1122–1132PubMedPubMedCentral
27.
Verkooijen HM, Peterse JL, Schipper MEI, Buskens E, Hendriks JHCL, Pijnappel RM et al (2003) Interobserver variability between general and expert pathologists during the histopathological assessment of large-core needle and open biopsies of non-palpable breast lesions. Eur J Cancer. 39(15):2187–2191PubMed
28.
29.
Kottner J, Audige L, Brorson S, Donner A, Gajewski BJ, Hroóbjartsson A et al (2011) Guidelines for Reporting Reliability and Agreement Studies (GRRAS) were proposed. Int J Nurs Stud. 48(6):661–671PubMed
30.
Elshof LE, Schaapveld M, Schmidt MK, Rutgers EJ, van Leeuwen FE, Wesseling J (2016) Subsequent risk of ipsilateral and contralateral invasive breast cancer after treatment for ductal carcinoma in situ: incidence and the effect of radiotherapy in a population-based cohort of 10,090 women. Breast Cancer Res Treat 159(3):553–563PubMedPubMedCentral
31.
Casparie M, Tiebosch ATMG, Burger G, Blauwgeers H, Van De Pol A, Van Krieken JHJM et al (2007) Pathology databanking and biobanking in The Netherlands, a central role for PALGA, the nationwide histopathology and cytopathology data network and archive. Cell Oncol 29(1):19–24PubMedPubMedCentral
32.
Barlow WE, Ichikawa L, Rosner D, Izumi S (1999) Analysis of case-cohort designs. J Clin Epidemiol 52(12):1165–1172PubMed
33.
Hayes AF, Krippendorff K (2007) Answering the call for a standard reliability measure for coding data. Commun Methods Meas 1(1):77–89
34.
Gwet KL (2014) Handbook of inter-rater reliability: the definitive guide to measuring the extent of agreement among raters, 4th edn. Advanced Analytics, LLC, Gaithersburg
35.
Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33(1):159–174PubMed
36.
Correa C, McGale P, Taylor C, Davidson N, Gelber R, Piccart M et al (2010) Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast. J Natl Cancer Inst 41(41):162–177
37.
Donker M, Litière S, Werutsky G, Julien JP, Fentiman IS, Agresti R et al (2013) Breast-conserving treatment with or without radiotherapy in ductal carcinoma in situ: 15-year recurrence rates and outcome after a recurrence, from the EORTC 10853 randomized phase III trial. J Clin Oncol 31(32):4054–4059PubMed
38.
Elshof LE, Tryfonidis K, Slaets L, Van Leeuwen-Stok AE, Skinner VP, Dif N et al (2015) Feasibility of a prospective, randomised, open-label, international multicentre, phase III, non-inferiority trial to assess the safety of active surveillance for low risk ductal carcinoma in situ: The LORD study. Eur J Cancer 51(12):1497–1510PubMed
39.
Francis A, Thomas J, Fallowfield L, Wallis M, Bartlett JMS, Brookes C et al (2015) Addressing overtreatment of screen detected DCIS. The LORIS trial. Eur J Cancer 51(16):2296–2303PubMed
40.
Hwang ES, Hyslop T, Lynch T, Frank E, Pinto D, Basila D et al (2019) The COMET (Comparison of Operative versus Monitoring and Endocrine Therapy) trial: a phase III randomised controlled clinical trial for low-risk ductal carcinoma in situ (DCIS). BMJ Open 9(3):e026797PubMedPubMedCentral
41.
Gwet KL (2008) Computing inter-rater reliability and its variance in the presence of high agreement. Br J Math Stat Psychol 61(1):29–48PubMed
42.
Bloom HJ, Richardson WW (1957) Histological grading and prognosis in breast cancer a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer 11(3):359–377PubMedPubMedCentral
43.
Elston CW, Ellis IO (1991) The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19(5):403–410PubMed
44.
Van Bockstal M, Baldewijns M, Colpaert C, Dano H, Floris G, Galant C et al (2018) Dichotomous histopathological assessment of ductal carcinoma in situ of the breast results in substantial interobserver concordance. Histopathology 73(6):923–932PubMed
45.
Dano H, Altinay S, Arnould L, Bletard N, Colpaert C, Dedeurwaerdere F et al (2019) Interobserver variability in upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast: the DCISion study. Mod Pathol 33(3):354–366PubMedPubMedCentral
46.
Visser LL, Elshof LE, Schaapveld M, Van De Vijver K, Groen EJ, Almekinders MM et al (2018) Clinicopathological risk factors for an invasive breast cancer recurrence after ductal carcinoma in situ-a nested case-control study. Clin Cancer Res 24(15):3593–3601PubMed
47.
Kerlikowske K, Molinaro AM, Gauthier ML, Berman HK, Waldman F, Bennington J et al (2010) Biomarker expression and risk of subsequent tumors after initial ductal carcinoma in situ diagnosis. J Natl Cancer Inst 102(9):627–637PubMedPubMedCentral
48.
Mohammed ZMA, McMillan DC, Elsberger B, Going JJ, Orange C, Mallon E et al (2012) Comparison of visual and automated assessment of Ki-67 proliferative activity and their impact on outcome in primary operable invasive ductal breast cancer. Br J Cancer 106(2):383–388PubMedPubMedCentral
49.
Van Velthuysen MLF, Groen EJ, Sanders J, Prins FA, Van Der Noort V, Korse CM (2014) Reliability of proliferation assessment by Ki-67 expression in neuroendocrine neoplasms: eyeballing or image analysis? Neuroendocrinology 100(4):288–292PubMed
50.
Stasik CJ, Davis M, Kimler BF, Fan F, Damjanov I, Thomas P et al (2011) Grading ductal carcinoma in situ of the breast using an automated proliferation index. Ann Clin Lab Sci 41(2):122–130PubMed
51.
52.
53.
Klimov S, Miligy IM, Gertych A, Jiang Y, Toss MS, Rida P et al (2019) A whole slide image-based machine learning approach to predict ductal carcinoma in situ (DCIS) recurrence risk. Breast Cancer Res 21(1):1–19
54.
Collins LC, Achacoso N, Haque R, Nekhlyudov L, Fletcher SW, Quesenberry CP et al (2013) Risk factors for non-invasive and invasive local recurrence in patients with ductal carcinoma in situ. Breast Cancer Res Treat 139(2):453–460PubMedPubMedCentral
Metadata
Title
Prognostic value of histopathological DCIS features in a large-scale international interrater reliability study
Authors
Emma J. Groen
Jan Hudecek
Lennart Mulder
Maartje van Seijen
Mathilde M. Almekinders
Stoyan Alexov
Anikó Kovács
Ales Ryska
Zsuzsanna Varga
Francisco-Javier Andreu Navarro
Simonetta Bianchi
Willem Vreuls
Eva Balslev
Max V. Boot
Janina Kulka
Ewa Chmielik
Ellis Barbé
Mathilda J. de Rooij
Winand Vos
Andrea Farkas
Natalja E. Leeuwis-Fedorovich
Peter Regitnig
Pieter J. Westenend
Loes F. S. Kooreman
Cecily Quinn
Giuseppe Floris
Gábor Cserni
Paul J. van Diest
Esther H. Lips
Michael Schaapveld
Jelle Wesseling
Grand Challenge PRECISION consortium
Publication date
01-10-2020
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-020-05816-x

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