Significant inter- and intra-laboratory variation in grading of invasive breast cancer: A nationwide study of 33,043 patients in the Netherlands

Int J Cancer. 2020 Feb 1;146(3):769-780. doi: 10.1002/ijc.32330. Epub 2019 Apr 29.

Abstract

Accurate, consistent and reproducible grading by pathologists is of key-importance for identification of individual patients with invasive breast cancer (IBC) that will or will not benefit from adjuvant systemic treatment. We studied the laboratory-specific grading variation using nationwide real-life data to create insight and awareness in grading variation. Synoptic pathology reports of all IBC resection-specimens, obtained between 2013 and 2016, were retrieved from the nationwide Dutch Pathology Registry (PALGA). Absolute differences in laboratory-proportions of Grades I-III were compared to the national reference. Multivariable logistic regression provided laboratory-specific odds ratios (ORs) for high- vs. low-grade IBC. 33,792 IBC pathology reports of 33,043 patients from 39 laboratories were included, of which 28.1% were reported as Grade I (range between laboratories 16.3-43.3%), 47.6% as Grade II (38.4-57.8%), and 24.3% as Grade III (15.5-34.3%). Based on national guidelines, the indication for adjuvant chemotherapy was dependent on histologic grade in 29.9% of patients. After case-mix correction, 20 laboratories (51.3%) showed a significantly deviant OR. Significant grading differences were also observed among pathologists within laboratories. In this cohort of 33,043 breast cancer patients, we observed substantial inter- and intra-laboratory variation in histologic grading. It can be anticipated that this has influenced outcome including exposure to unnecessary toxicity, since choice of adjuvant chemotherapy was dependent on grade in nearly a third of patients. Better standardization and training seems warranted.

Keywords: histologic grade; invasive breast cancer; pathology; patient management; prognostic factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Breast / pathology*
  • Breast / surgery
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Chemotherapy, Adjuvant / adverse effects
  • Chemotherapy, Adjuvant / methods
  • Cohort Studies
  • Female
  • Humans
  • Laboratories / standards
  • Laboratories / statistics & numerical data*
  • Mastectomy
  • Middle Aged
  • Neoplasm Grading
  • Netherlands
  • Observer Variation
  • Pathologists / standards
  • Pathologists / statistics & numerical data
  • Pathology / standards
  • Pathology / statistics & numerical data*
  • Patient Selection*
  • Practice Guidelines as Topic
  • Registries / statistics & numerical data