Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Acs, Balazs, Fredriksson, Irma, Rönnlund, Caroline, Hagerling, Catharina, Ehinger, Anna, Kovács, Anikó, Røge, Rasmus, Bergh, Jonas, Hartman, Johan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963154/
https://www.ncbi.nlm.nih.gov/pubmed/33803148
http://dx.doi.org/10.3390/cancers13051166
_version_ 1783665576811429888
author Acs, Balazs
Fredriksson, Irma
Rönnlund, Caroline
Hagerling, Catharina
Ehinger, Anna
Kovács, Anikó
Røge, Rasmus
Bergh, Jonas
Hartman, Johan
author_facet Acs, Balazs
Fredriksson, Irma
Rönnlund, Caroline
Hagerling, Catharina
Ehinger, Anna
Kovács, Anikó
Røge, Rasmus
Bergh, Jonas
Hartman, Johan
author_sort Acs, Balazs
collection PubMed
description 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. 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.
format Online
Article
Text
id pubmed-7963154
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-79631542021-03-17 Variability in Breast Cancer Biomarker Assessment and the Effect on Oncological Treatment Decisions: A Nationwide 5-Year Population-Based Study Acs, Balazs Fredriksson, Irma Rönnlund, Caroline Hagerling, Catharina Ehinger, Anna Kovács, Anikó Røge, Rasmus Bergh, Jonas Hartman, Johan Cancers (Basel) Article 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. 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. MDPI 2021-03-09 /pmc/articles/PMC7963154/ /pubmed/33803148 http://dx.doi.org/10.3390/cancers13051166 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Acs, Balazs
Fredriksson, Irma
Rönnlund, Caroline
Hagerling, Catharina
Ehinger, Anna
Kovács, Anikó
Røge, Rasmus
Bergh, Jonas
Hartman, Johan
Variability in Breast Cancer Biomarker Assessment and the Effect on Oncological Treatment Decisions: A Nationwide 5-Year Population-Based Study
title Variability in Breast Cancer Biomarker Assessment and the Effect on Oncological Treatment Decisions: A Nationwide 5-Year Population-Based Study
title_full Variability in Breast Cancer Biomarker Assessment and the Effect on Oncological Treatment Decisions: A Nationwide 5-Year Population-Based Study
title_fullStr Variability in Breast Cancer Biomarker Assessment and the Effect on Oncological Treatment Decisions: A Nationwide 5-Year Population-Based Study
title_full_unstemmed Variability in Breast Cancer Biomarker Assessment and the Effect on Oncological Treatment Decisions: A Nationwide 5-Year Population-Based Study
title_short Variability in Breast Cancer Biomarker Assessment and the Effect on Oncological Treatment Decisions: A Nationwide 5-Year Population-Based Study
title_sort variability in breast cancer biomarker assessment and the effect on oncological treatment decisions: a nationwide 5-year population-based study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963154/
https://www.ncbi.nlm.nih.gov/pubmed/33803148
http://dx.doi.org/10.3390/cancers13051166
work_keys_str_mv AT acsbalazs variabilityinbreastcancerbiomarkerassessmentandtheeffectononcologicaltreatmentdecisionsanationwide5yearpopulationbasedstudy
AT fredrikssonirma variabilityinbreastcancerbiomarkerassessmentandtheeffectononcologicaltreatmentdecisionsanationwide5yearpopulationbasedstudy
AT ronnlundcaroline variabilityinbreastcancerbiomarkerassessmentandtheeffectononcologicaltreatmentdecisionsanationwide5yearpopulationbasedstudy
AT hagerlingcatharina variabilityinbreastcancerbiomarkerassessmentandtheeffectononcologicaltreatmentdecisionsanationwide5yearpopulationbasedstudy
AT ehingeranna variabilityinbreastcancerbiomarkerassessmentandtheeffectononcologicaltreatmentdecisionsanationwide5yearpopulationbasedstudy
AT kovacsaniko variabilityinbreastcancerbiomarkerassessmentandtheeffectononcologicaltreatmentdecisionsanationwide5yearpopulationbasedstudy
AT røgerasmus variabilityinbreastcancerbiomarkerassessmentandtheeffectononcologicaltreatmentdecisionsanationwide5yearpopulationbasedstudy
AT berghjonas variabilityinbreastcancerbiomarkerassessmentandtheeffectononcologicaltreatmentdecisionsanationwide5yearpopulationbasedstudy
AT hartmanjohan variabilityinbreastcancerbiomarkerassessmentandtheeffectononcologicaltreatmentdecisionsanationwide5yearpopulationbasedstudy