Variability in Breast Cancer Biomarker Assessment and the Effect on Oncological Treatment Decisions: A Nationwide 5-Year Population-Based Study
1
Department of Oncology and Pathology, Karolinska Institutet, 17176 Stockholm, Sweden
2
Department of Clinical Pathology and Cytology, Karolinska University Laboratory, 11883 Stockholm, Sweden
3
Department of Breast, Endocrine Tumors and Sarcoma, Karolinska University Hospital, 17176 Stockholm, Sweden
4
Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176 Stockholm, Sweden
5
Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, 22185 Lund, Sweden
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Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, 22184 Lund, Sweden
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Department of Clinical Pathology, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden
8
Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark
9
NordiQC, Institute of Pathology, Aalborg University Hospital, 9000 Aalborg, Denmark
10
Breast Center, Cancer Theme, Karolinska University Hospital and Karolinska Comprehensive Cancer Center, Gävlegatan 55, 17164 Solna, Sweden
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Academic Editor: Rupert Bartsch
Cancers 2021, 13(5), 1166; https://doi.org/10.3390/cancers13051166
Received: 1 January 2021
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Revised: 24 February 2021
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Accepted: 26 February 2021
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Published: 9 March 2021
(This article belongs to the Special Issue Novel Biomarkers: Validity, Evaluation and Biological Roles for Breast Cancer)
Simple Summary
Biomarkers that define breast cancer treatment recommendations include estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth-factor receptor 2 (HER2); histological grade; and in many countries, the Ki67 proliferation index. However, the subjective nature and degree of variability in breast cancer biomarker assessment might result in under- or overtreatment. We demonstrated that limited variability exists in ER, PR, and HER2 positivity rates among 29 departments in Sweden, including 43,261 patients. However, even a few outlier labs affect endocrine and anti-HER2 treatment rates in a clinically relevant proportion, indicating a need for improvement. Despite international guidelines, standardized protocols, and external quality control procedures, very high variability was found in Ki67 scoring and histological grading, indicating a need for new methods. Monitoring rates of biomarker expression and treatments among departments should be mandatory in order to detect variability issues affecting the clinical management of breast cancer.
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.
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Keywords:
positivity rate; biomarker; breast cancer; endocrine treatment; HER2-targeted treatment; variability
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MDPI and ACS Style
Acs, B.; Fredriksson, I.; Rönnlund, C.; Hagerling, C.; Ehinger, A.; Kovács, A.; Røge, R.; Bergh, J.; Hartman, J. Variability in Breast Cancer Biomarker Assessment and the Effect on Oncological Treatment Decisions: A Nationwide 5-Year Population-Based Study. Cancers 2021, 13, 1166. https://doi.org/10.3390/cancers13051166
AMA Style
Acs B, Fredriksson I, Rönnlund C, Hagerling C, Ehinger A, Kovács A, Røge R, Bergh J, Hartman J. Variability in Breast Cancer Biomarker Assessment and the Effect on Oncological Treatment Decisions: A Nationwide 5-Year Population-Based Study. Cancers. 2021; 13(5):1166. https://doi.org/10.3390/cancers13051166
Chicago/Turabian StyleAcs, Balazs, Irma Fredriksson, Caroline Rönnlund, Catharina Hagerling, Anna Ehinger, Anikó Kovács, Rasmus Røge, Jonas Bergh, and Johan Hartman. 2021. "Variability in Breast Cancer Biomarker Assessment and the Effect on Oncological Treatment Decisions: A Nationwide 5-Year Population-Based Study" Cancers 13, no. 5: 1166. https://doi.org/10.3390/cancers13051166
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