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. 2021 Mar 9;13(5):1166.
doi: 10.3390/cancers13051166.

Variability in Breast Cancer Biomarker Assessment and the Effect on Oncological Treatment Decisions: A Nationwide 5-Year Population-Based Study

Balazs Acs  1   2 , Irma Fredriksson  3   4 , Caroline Rönnlund  1   2 , Catharina Hagerling  5 , Anna Ehinger  5   6 , Anikó Kovács  7 , Rasmus Røge  8   9 , Jonas Bergh  1   10 , Johan Hartman  1   2
Affiliations

Variability in Breast Cancer Biomarker Assessment and the Effect on Oncological Treatment Decisions: A Nationwide 5-Year Population-Based Study

Balazs Acs et al. Cancers (Basel). .

Abstract

We compared estrogen receptor (ER), progesterone receptor (PR), human epidermal growth-factor receptor 2 (HER2), Ki67, and grade scores among the pathology departments in Sweden. We investigated how ER and HER2 positivity rates affect the distribution of endocrine and HER2-targeted treatments among oncology departments. All breast cancer patients diagnosed between 2013 and 2018 in Sweden were identified in the National Quality Register for Breast Cancer. Cases with data on ER, PR, HER2, Ki67, grade, and treatment were selected (43,261 cases from 29 departments following the guidelines for biomarker testing). The ER positivity rates ranged from 84.2% to 97.6% with 6/29 labs out of the overall confidence intervals (CIs), while PR rates varied between 64.8% and 86.6% with 7/29 labs out of the CIs. HER2 positivity rates ranged from 9.4% to 16.3%, with 3/29 labs out of the overall CIs. Median Ki67 varied between 15% and 30%, where 19/29 labs showed significant intra-laboratory variability. The proportion of grade-II cases varied between 42.9% and 57.1%, and 13/29 labs were outside of the CI. Adjusting for patient characteristics, the proportion of endocrine and anti-HER2 treatments followed the rate of ER and HER2 positivity, illustrating the clinical effect of inter- and intra-laboratory variability. There was limited variability among departments in ER, PR, and HER2 testing. However, even a few outlier pathology labs affected endocrine and HER2-targeted treatment rates in a clinically relevant proportion, suggesting the need for improvement. High variability was found in grading and Ki67 assessment, illustrating the need for the adoption of new technologies in practice.

Keywords: HER2-targeted treatment; biomarker; breast cancer; endocrine treatment; positivity rate; variability.

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Conflict of interest statement

J.H. was former member of the advisory board at Visiopharm A/S. J.H. has obtained speaker’s honoraria or advisory board remunerations from Roche, Novartis, AstraZeneca, Eli Lilly, Pfizer and MSD. J.H. is co-founder and shareholder of Stratipath AB. J.H. has received institutional research grants from Cepheid and Novartis. Other authors have no conflicts of interest to disclose. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Endocrine receptor (ER) status and endocrine treatment between 2013 and 2018 by department. Dashed lines represent the CI for overall positivity (blue) and overall treatment rate (red). (A) includes all the patients while (B) shows results with cases ≥10 mm T size, ≤70 years of age.
Figure 2
Figure 2
Intra-lab variability for ER (A) and human epidermal growth-factor receptor 2 (HER2) (B) status among pathology departments. Only laboratories showing statistically significant differences are shown. Please refer to Figure S1 to see all the labs.
Figure 3
Figure 3
HER2 status and anti-HER2 treatment between 2013 and 2018 by pathology department. Dashed lines represent the CI for overall positivity (blue) and overall treatment rate (red). (A) includes all the patients while (B) shows results with cases ≥10 mm T size, ≤70 years of age.
Figure 4
Figure 4
Inter- (A) and intra-laboratory variability (B) for Ki67 among 29 pathology departments.
Figure 5
Figure 5
Inter- (A) and intra-laboratory variability (B) for histological grade status among 29 pathology departments.
See this image and copyright information in PMC

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