Cargando…

A Standardized Investigational Ki-67 Immunohistochemistry Assay Used to Assess High-Risk Early Breast Cancer Patients in the monarchE Phase 3 Clinical Study Identifies a Population With Greater Risk of Disease Recurrence When Treated With Endocrine Therapy Alone

The objectives were to develop a standardized Ki-67 immunohistochemistry (IHC) method for precise, robust, and reproducible assessment of patients with early breast cancer, and utilize this assay to evaluate patients participating in the monarchE study (NCT03155997). The Ki-67 assay was developed an...

Descripción completa

Detalles Bibliográficos
Autores principales: Polewski, Monika D., Nielsen, Gitte B., Gu, Ying, Weaver, Aaron T., Gegg, Gavin, Tabuena-Frolli, Siena, Cajaiba, Mariana, Hanks, Debra, Method, Michael, Press, Michael F., Gottstein, Claudia, Gruver, Aaron M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989635/
https://www.ncbi.nlm.nih.gov/pubmed/35384873
http://dx.doi.org/10.1097/PAI.0000000000001009
_version_ 1784683219285704704
author Polewski, Monika D.
Nielsen, Gitte B.
Gu, Ying
Weaver, Aaron T.
Gegg, Gavin
Tabuena-Frolli, Siena
Cajaiba, Mariana
Hanks, Debra
Method, Michael
Press, Michael F.
Gottstein, Claudia
Gruver, Aaron M.
author_facet Polewski, Monika D.
Nielsen, Gitte B.
Gu, Ying
Weaver, Aaron T.
Gegg, Gavin
Tabuena-Frolli, Siena
Cajaiba, Mariana
Hanks, Debra
Method, Michael
Press, Michael F.
Gottstein, Claudia
Gruver, Aaron M.
author_sort Polewski, Monika D.
collection PubMed
description The objectives were to develop a standardized Ki-67 immunohistochemistry (IHC) method for precise, robust, and reproducible assessment of patients with early breast cancer, and utilize this assay to evaluate patients participating in the monarchE study (NCT03155997). The Ki-67 assay was developed and validated for sensitivity, specificity, repeatability, precision, and robustness using a predefined ≥20% cutoff. Reproducibility studies (intersite and intrasite, interobserver and intraobserver) were conducted at 3 external laboratories using detailed scoring instructions designed for monarchE. Using the assay, patient tumors were classified as displaying high (≥20%) or low (<20%) Ki-67 expression; Kaplan-Meier methods evaluated 2-year invasive disease-free survival rates for these 2 groups among patients treated with endocrine therapy (ET) alone. All analytical validation and reproducibility studies achieved point estimates of >90% for negative, positive, and overall percent agreement. Intersite reproducibility produced point estimate values of 94.7%, 100.0%, and 97.3%. External interobserver reproducibility produced point estimate values of 98.9%, 97.8%, and 98.3%. Among 1954 patients receiving ET alone, 986 (50.5%) had high and 968 (49.5%) had low Ki-67 expression. Patients with high Ki-67 had a clinically meaningful increased risk of developing invasive disease within 2 years compared with those with low Ki-67 [2-y invasive disease-free survival rate: 86.1% (95% confidence interval: 83.1%-88.7%) vs. 92.0% (95% confidence interval: 89.7%-93.9%), respectively]. This standardized Ki-67 methodology resulted in high concordance across multiple laboratories, and its use in the monarchE study prospectively demonstrated the prognostic value of Ki-67 IHC in HR+, HER2− early breast cancer with high-risk clinicopathologic features.
format Online
Article
Text
id pubmed-8989635
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Lippincott Williams & Wilkins
record_format MEDLINE/PubMed
spelling pubmed-89896352022-04-13 A Standardized Investigational Ki-67 Immunohistochemistry Assay Used to Assess High-Risk Early Breast Cancer Patients in the monarchE Phase 3 Clinical Study Identifies a Population With Greater Risk of Disease Recurrence When Treated With Endocrine Therapy Alone Polewski, Monika D. Nielsen, Gitte B. Gu, Ying Weaver, Aaron T. Gegg, Gavin Tabuena-Frolli, Siena Cajaiba, Mariana Hanks, Debra Method, Michael Press, Michael F. Gottstein, Claudia Gruver, Aaron M. Appl Immunohistochem Mol Morphol Research Articles The objectives were to develop a standardized Ki-67 immunohistochemistry (IHC) method for precise, robust, and reproducible assessment of patients with early breast cancer, and utilize this assay to evaluate patients participating in the monarchE study (NCT03155997). The Ki-67 assay was developed and validated for sensitivity, specificity, repeatability, precision, and robustness using a predefined ≥20% cutoff. Reproducibility studies (intersite and intrasite, interobserver and intraobserver) were conducted at 3 external laboratories using detailed scoring instructions designed for monarchE. Using the assay, patient tumors were classified as displaying high (≥20%) or low (<20%) Ki-67 expression; Kaplan-Meier methods evaluated 2-year invasive disease-free survival rates for these 2 groups among patients treated with endocrine therapy (ET) alone. All analytical validation and reproducibility studies achieved point estimates of >90% for negative, positive, and overall percent agreement. Intersite reproducibility produced point estimate values of 94.7%, 100.0%, and 97.3%. External interobserver reproducibility produced point estimate values of 98.9%, 97.8%, and 98.3%. Among 1954 patients receiving ET alone, 986 (50.5%) had high and 968 (49.5%) had low Ki-67 expression. Patients with high Ki-67 had a clinically meaningful increased risk of developing invasive disease within 2 years compared with those with low Ki-67 [2-y invasive disease-free survival rate: 86.1% (95% confidence interval: 83.1%-88.7%) vs. 92.0% (95% confidence interval: 89.7%-93.9%), respectively]. This standardized Ki-67 methodology resulted in high concordance across multiple laboratories, and its use in the monarchE study prospectively demonstrated the prognostic value of Ki-67 IHC in HR+, HER2− early breast cancer with high-risk clinicopathologic features. Lippincott Williams & Wilkins 2022-04 2022-01-25 /pmc/articles/PMC8989635/ /pubmed/35384873 http://dx.doi.org/10.1097/PAI.0000000000001009 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle Research Articles
Polewski, Monika D.
Nielsen, Gitte B.
Gu, Ying
Weaver, Aaron T.
Gegg, Gavin
Tabuena-Frolli, Siena
Cajaiba, Mariana
Hanks, Debra
Method, Michael
Press, Michael F.
Gottstein, Claudia
Gruver, Aaron M.
A Standardized Investigational Ki-67 Immunohistochemistry Assay Used to Assess High-Risk Early Breast Cancer Patients in the monarchE Phase 3 Clinical Study Identifies a Population With Greater Risk of Disease Recurrence When Treated With Endocrine Therapy Alone
title A Standardized Investigational Ki-67 Immunohistochemistry Assay Used to Assess High-Risk Early Breast Cancer Patients in the monarchE Phase 3 Clinical Study Identifies a Population With Greater Risk of Disease Recurrence When Treated With Endocrine Therapy Alone
title_full A Standardized Investigational Ki-67 Immunohistochemistry Assay Used to Assess High-Risk Early Breast Cancer Patients in the monarchE Phase 3 Clinical Study Identifies a Population With Greater Risk of Disease Recurrence When Treated With Endocrine Therapy Alone
title_fullStr A Standardized Investigational Ki-67 Immunohistochemistry Assay Used to Assess High-Risk Early Breast Cancer Patients in the monarchE Phase 3 Clinical Study Identifies a Population With Greater Risk of Disease Recurrence When Treated With Endocrine Therapy Alone
title_full_unstemmed A Standardized Investigational Ki-67 Immunohistochemistry Assay Used to Assess High-Risk Early Breast Cancer Patients in the monarchE Phase 3 Clinical Study Identifies a Population With Greater Risk of Disease Recurrence When Treated With Endocrine Therapy Alone
title_short A Standardized Investigational Ki-67 Immunohistochemistry Assay Used to Assess High-Risk Early Breast Cancer Patients in the monarchE Phase 3 Clinical Study Identifies a Population With Greater Risk of Disease Recurrence When Treated With Endocrine Therapy Alone
title_sort standardized investigational ki-67 immunohistochemistry assay used to assess high-risk early breast cancer patients in the monarche phase 3 clinical study identifies a population with greater risk of disease recurrence when treated with endocrine therapy alone
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989635/
https://www.ncbi.nlm.nih.gov/pubmed/35384873
http://dx.doi.org/10.1097/PAI.0000000000001009
work_keys_str_mv AT polewskimonikad astandardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT nielsengitteb astandardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT guying astandardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT weaveraaront astandardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT gegggavin astandardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT tabuenafrollisiena astandardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT cajaibamariana astandardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT hanksdebra astandardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT methodmichael astandardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT pressmichaelf astandardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT gottsteinclaudia astandardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT gruveraaronm astandardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT polewskimonikad standardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT nielsengitteb standardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT guying standardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT weaveraaront standardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT gegggavin standardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT tabuenafrollisiena standardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT cajaibamariana standardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT hanksdebra standardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT methodmichael standardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT pressmichaelf standardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT gottsteinclaudia standardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone
AT gruveraaronm standardizedinvestigationalki67immunohistochemistryassayusedtoassesshighriskearlybreastcancerpatientsinthemonarchephase3clinicalstudyidentifiesapopulationwithgreaterriskofdiseaserecurrencewhentreatedwithendocrinetherapyalone