Abstract P4-02-13: Inter- and intra-laboratory variation in grading of invasive breast cancer: A nationwide study in the Netherlands
Authors: van Dooijeweert C , van Diest PJ , Willems SM , Kuijpers CC , Overbeek LI , Deckers IA 
Published: May 2019

Abstract
Background
Histologic grading is one of the best established prognostic factors in invasive breast cancer (IBC) and is used to guide patient management. Yet, the level of inter- and intra-observer agreement does not reach high enough clinical standards. To improve standardization, we aimed to gain insight into laboratory-specific variation in histologic grading.
Methods
All synoptic pathology reports of IBC resection specimens between 2013-2016 were retrieved from PALGA, the nationwide Dutch Pathology Registry. All lesions were graded according to the modified Bloom and Richardson guideline, which combines assessment of cell morphology (nuclear polymorphism), measurement of differentiation (tubular differentiation) and assessment of proliferation (mitotic count). Absolute differences in proportions of grade I-III and the three components of grading between laboratories were compared to the national distributions. For logistic regression analyses, grade was dichotomized into high- and low-grade by two alternative definitions for high-grade IBC (either solely grade III or grade II-III). Multivariable logistic regression, to correct for case mix (age, tumor size, type of surgery, histologic subtype, ER/PR-receptor status, HER2-receptor status), provided two laboratory-specific odds ratios (ORs) and 95% confidence intervals (CI) for high versus low-grade IBC compared to the reference laboratory.
Findings
In total 33.792 IBC cases from 39 laboratories were included, of which 28.1% were reported as grade I (range 16.3-43.3%), 47.6% as grade II (range 38.4-57.8%), and 24.3% as grade III (range 15.5-34.3%). More than half of the laboratories (22/39) showed proportions outside the 95% confidence limits of the national proportion for both grade I and grade III, followed by 41.0% of the laboratories for grade II. After case mix correction, 20 laboratories (51.3%) showed at least one significantly higher or lower OR than the reference laboratory. Four laboratories (10.3%) showed significantly deviant ORs on both analyses. Most variation between laboratories was observed for nuclear polymorphism. Significant grading differences were also observed between pathologists within 62.5% of the laboratories that could be analyzed. Overall, the indication for adjuvant chemotherapy was dependent on histologic grade in 29.9% of patients.
Conclusion
We observed substantial inter- and intra-laboratory variation in the histologic grading of IBC, which may likely influence treatment decisions and subsequently patient outcome as the indication for chemotherapy depends on histologic grade in almost every one in three patients.
Citation Format: van Dooijeweert C, van Diest PJ, Willems SM, Kuijpers CC, Overbeek LI, Deckers IA. Inter- and intra-laboratory variation in grading of invasive breast cancer: A nationwide study in the Netherlands [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-02-13.