1. Prognostic value of histopathological DCIS features in a large-scale international interrater reliability study
- Author
-
Jan Hudecek, Max V. Boot, Lennart Mulder, Winand Vos, Ellis Barbé, Zsuzsanna Varga, Natalja E. Leeuwis-Fedorovich, Esther H. Lips, Emma J. Groen, Willem Vreuls, Mathilda J. de Rooij, Giuseppe Floris, Paul J. van Diest, Gábor Cserni, Ales Ryska, Francisco Javier Andreu Navarro, Peter Regitnig, Anikó Kovács, Jelle Wesseling, Stoyan Alexov, Cecily Quinn, Eva Balslev, Mathilde M. Almekinders, Maartje van Seijen, Pieter J. Westenend, Ewa Chmielik, Simonetta Bianchi, Janina Kulka, Loes F. S. Kooreman, Andrea Farkas, Michael Schaapveld, Pathology, MUMC+: DA Pat Pathologie (9), and RS: GROW - R2 - Basic and Translational Cancer Biology
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Epidemiology ,CARCINOMA-IN-SITU ,Breast Neoplasms ,LOCAL RECURRENCE ,Mastectomy, Segmental ,CLASSIFICATION ,Lymphocytic Infiltrate ,Breast cancer ,Internal medicine ,REPRODUCIBILITY ,Medicine ,Humans ,Grading (tumors) ,Risk stratification ,INVASIVE BREAST-CANCER ,RISK ,Science & Technology ,business.industry ,Proportional hazards model ,Hazard ratio ,Carcinoma, Ductal, Breast ,Ductal carcinoma in situ ,PROLIFERATION ,Reproducibility of Results ,Ductal carcinoma ,medicine.disease ,Prognosis ,PHASE-III ,Confidence interval ,Interrater reliability ,Carcinoma, Intraductal, Noninfiltrating ,AGREEMENT ,Cohort ,Female ,Neoplasm Recurrence, Local ,business ,PATHOLOGISTS ,Life Sciences & Biomedicine ,Invasive breast cancer - 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.
- Published
- 2020
- Full Text
- View/download PDF