Inter- and intra-laboratory variation in grading of invasive breast cancer: a nationwide study of 33,043 patients in the Netherlands Carmen van Dooijeweert European Congress of Pathology MD, PhD-student September 7-11, 2019 Nice c.vandooijeweert-3@umcutrecht.nl
I hereby declare that I have no conflict of interest
Breast cancer: background Most common type of cancer in European women 1 • Breast cancer management: it all starts with pathology • – Subtype: PATHOLOGY – Prognosis: PATHOLOGY – Treatment: PATHOLOGY 1. International Agency for Research on Cancer (WHO), source: GLOBOCON 2018
Breast cancer biomarkers Histologic grade • – B&R (modified) – Clinical decisions • Chemotherapy • Radiotherapy • Gene-expression profiling
Reproducibility histologic grading • No more than moderate 1-4 But how are we doing in daily clinical practice? 1. Boiesen et al. Acta Oncol 2000: 39(1):41-45 2. Frierson et al. Am J Clin Pathol 1995:103(2):195-198 3. Italian Network for Quality Assurance of Tumour Biomarkers (INQAT group). Pathologica 2005:97(1):1-6 4. Meyer et al. Mod Pathol 2005:18(8):1067-1078
Real-life data on a Dutch nationwide level the nationwide network and registry of histo- and cytopathology in the Netherlands Synoptic reporting • Increased overall completeness of reports 1 ▪ Easy data extraction ▪ Breast cancer resection specimens: 80% via synoptic protocol 2 ▪ 1. Sluijter et al. Virchows Archiv 2016:468(4):639-649. 2. PALGA Foundation, Annual Report 2018
Grading in the Netherlands; 2013-2016 (n=33,792) Laboratory-level (n=39) Mean: 28.1% Grade I Range: 16.3-43.3% 60% 50% Proportion (%) grade I 40% 30% 20% 10% 0% 0 500 1000 1500 2000 2500 Number of IBC reports per laboratory Case-mix: age, tumour size, type of surgery, histologic subtype, ER/PR- and, HER2-receptor status
Grading in the Netherlands; 2013-2016 (n=33,792) Laboratory-level (n=39) Mean: 47.6% Grade II Range: 38.4-57.8% 60% Proportion (%) grade II 50% 40% 30% 20% 10% 0% 0 500 1000 1500 2000 2500 Number of IBC reports per laboratory Mean: 24.3% Grade III Range: 15.5-34.3% 60% Proportion (%) grade III 50% 40% 30% 20% 10% 0% 0 500 1000 1500 2000 2500 Number of IBC reports per laboratory
Grading in the Netherlands; 2013-2016 Pathologist-level (n=68, 8 laboratories) Grade I 60% 50% Proportion (%) grade I 40% 30% 20% 10% 0% 0 50 100 150 200 250 300 Number of IBC reports per pathologist
Grading in the Netherlands; 2013-2016 Pathologist-level (n=68, 8 laboratories) 80% Grade II Proportion (%) grade II 70% 60% 50% 40% 30% 20% 0 50 100 150 200 250 300 Number of IBC reports per pathologist 60% Grade III Proportion (%) grade III 50% 40% 30% 20% 10% 0% 0 50 100 150 200 250 300 Number of IBC reports per pathologist
Grading variation; does it really matter? Chemotherapy (n=19,461) n = 5,821 According to the Dutch breast cancer guideline, adjuvant chemotherapy (aCT) Invasive breast cancer reports with complete is advised for patients with a positive lymph node status (N+) and for patients information on all relevant variables (i.e. lymph with a negative lymph node status (N0) with the following characteristics: node status (N), age, tumor size, histologic grade) n = 19,461 · Age <35 years, except for a grade I tumor <1cm · Age ≥ 35 years with a tumor of 1.1-2 cm and ≥grade II , or a tumor >2cm All patients: 29.9% • · HER2 overexpression in a tumor ≥ 0.5cm N0 N+ N0-patients: 44.5% • n = 13,077 n = 6,384 aCT HER2 - HER2 + n = 11,958 n = 1,119 ≤ 2.0 cm ≥ 0.5 cm > 2.0 cm <0.5 cm n = 9,353 n = 2,605 n = 43 n = 1,076 aCT aCT ≥ 35 years <35 years ≥ 35 years <35 years n = 72 n = 9,281 n = 3 n = 40 Grade I: no aCT no aCT ≤ 1 cm ≤ 1 cm > 1 cm 1.1-2 cm Grade II-III: aCT n = 27 n = 45 n = 3,490 n = 5,791 Grade I: no aCT Grade I: no aCT aCT no aCT Grade II-III: aCT Grade II-III: aCT Curigliano et al. Ann Oncol 2017: 28(8):1700-1712
Conclusion: histologic grading Synoptic pathology reports of > 33,000 patients • Substantial inter- and intra-laboratory variation in grading of invasive breast cancer in • daily clinical practice Not explained by differences in case-mix – Biomarker of major clinical importance • Indication chemotherapy – 1 in 3 breast cancer patients • 1 in 2 lymph-node negative breast cancer patients • Decrease in variation warranted! • Interventions • Feedback reports – E-learning –
Acknowledgements Paul van Diest Carolien van Deurzen Elsken van der Wall Henk-Jan van Slooten Stefan Willems Jelle Wesseling Chantal Kuijpers Pieter Westenend Inge Baas Ivette Deckers Lucy Overbeek
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