Cargando…

Clinical validation of an immunohistochemistry‐based CanAssist‐Breast test for distant recurrence prediction in hormone receptor‐positive breast cancer patients

CanAssist‐Breast (CAB) is an immunohistochemistry (IHC)‐based prognostic test for early‐stage Hormone Receptor (HR+)‐positive breast cancer patients. CAB uses a Support Vector Machine (SVM) trained algorithm which utilizes expression levels of five biomarkers (CD44, ABCC4, ABCC11, N‐Cadherin, and Pa...

Descripción completa

Detalles Bibliográficos
Autores principales: Bakre, Manjiri M., Ramkumar, Charusheila, Attuluri, Arun Kumar, Basavaraj, Chetana, Prakash, Chandra, Buturovic, Ljubomir, Madhav, Lekshmi, Naidu, Nirupama, R, Prathima, Somashekhar, S. P., Gupta, Sudeep, Doval, Dinesh Chandra, Pegram, Mark D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488210/
https://www.ncbi.nlm.nih.gov/pubmed/30848103
http://dx.doi.org/10.1002/cam4.2049
_version_ 1783414623897124864
author Bakre, Manjiri M.
Ramkumar, Charusheila
Attuluri, Arun Kumar
Basavaraj, Chetana
Prakash, Chandra
Buturovic, Ljubomir
Madhav, Lekshmi
Naidu, Nirupama
R, Prathima
Somashekhar, S. P.
Gupta, Sudeep
Doval, Dinesh Chandra
Pegram, Mark D.
author_facet Bakre, Manjiri M.
Ramkumar, Charusheila
Attuluri, Arun Kumar
Basavaraj, Chetana
Prakash, Chandra
Buturovic, Ljubomir
Madhav, Lekshmi
Naidu, Nirupama
R, Prathima
Somashekhar, S. P.
Gupta, Sudeep
Doval, Dinesh Chandra
Pegram, Mark D.
author_sort Bakre, Manjiri M.
collection PubMed
description CanAssist‐Breast (CAB) is an immunohistochemistry (IHC)‐based prognostic test for early‐stage Hormone Receptor (HR+)‐positive breast cancer patients. CAB uses a Support Vector Machine (SVM) trained algorithm which utilizes expression levels of five biomarkers (CD44, ABCC4, ABCC11, N‐Cadherin, and Pan‐Cadherin) and three clinical parameters such as tumor size, grade, and node status as inputs to generate a risk score and categorizes patients as low‐ or high‐risk for distant recurrence within 5 years of diagnosis. In this study, we present clinical validation of CAB. CAB was validated using a retrospective cohort of 857 patients. All patients were treated either with endocrine therapy or chemoendocrine therapy. Risk categorization by CAB was analyzed by calculating Distant Metastasis‐Free Survival (DMFS) and recurrence rates using Kaplan‐Meier survival curves. Multivariate analysis was performed to calculate Hazard ratios (HR) for CAB high‐risk vs low‐risk patients. The results showed that Distant Metastasis‐Free Survival (DMFS) was significantly different (P‐0.002) between low‐ (DMFS: 95%) and high‐risk (DMFS: 80%) categories in the endocrine therapy treated alone subgroup (n = 195) as well as in the total cohort (n = 857, low‐risk DMFS: 95%, high‐risk DMFS: 84%, P < 0.0001). In addition, the segregation of the risk categories was significant (P = 0.0005) in node‐positive patients, with a difference in DMFS of 12%. In multivariate analysis, CAB risk score was the most significant predictor of distant recurrence with hazard ratio of 3.2048 (P < 0.0001). CAB stratified patients into discrete risk categories with high statistical significance compared to Ki‐67 and IHC4 score‐based stratification. CAB stratified a higher percentage of the cohort (82%) as low‐risk than IHC4 score (41.6%) and could re‐stratify >74% of high Ki‐67 and IHC4 score intermediate‐risk zone patients into low‐risk category. Overall the data suggest that CAB can effectively predict risk of distant recurrence with clear dichotomous high‐ or low‐risk categorization.
format Online
Article
Text
id pubmed-6488210
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-64882102019-05-23 Clinical validation of an immunohistochemistry‐based CanAssist‐Breast test for distant recurrence prediction in hormone receptor‐positive breast cancer patients Bakre, Manjiri M. Ramkumar, Charusheila Attuluri, Arun Kumar Basavaraj, Chetana Prakash, Chandra Buturovic, Ljubomir Madhav, Lekshmi Naidu, Nirupama R, Prathima Somashekhar, S. P. Gupta, Sudeep Doval, Dinesh Chandra Pegram, Mark D. Cancer Med Cancer Biology CanAssist‐Breast (CAB) is an immunohistochemistry (IHC)‐based prognostic test for early‐stage Hormone Receptor (HR+)‐positive breast cancer patients. CAB uses a Support Vector Machine (SVM) trained algorithm which utilizes expression levels of five biomarkers (CD44, ABCC4, ABCC11, N‐Cadherin, and Pan‐Cadherin) and three clinical parameters such as tumor size, grade, and node status as inputs to generate a risk score and categorizes patients as low‐ or high‐risk for distant recurrence within 5 years of diagnosis. In this study, we present clinical validation of CAB. CAB was validated using a retrospective cohort of 857 patients. All patients were treated either with endocrine therapy or chemoendocrine therapy. Risk categorization by CAB was analyzed by calculating Distant Metastasis‐Free Survival (DMFS) and recurrence rates using Kaplan‐Meier survival curves. Multivariate analysis was performed to calculate Hazard ratios (HR) for CAB high‐risk vs low‐risk patients. The results showed that Distant Metastasis‐Free Survival (DMFS) was significantly different (P‐0.002) between low‐ (DMFS: 95%) and high‐risk (DMFS: 80%) categories in the endocrine therapy treated alone subgroup (n = 195) as well as in the total cohort (n = 857, low‐risk DMFS: 95%, high‐risk DMFS: 84%, P < 0.0001). In addition, the segregation of the risk categories was significant (P = 0.0005) in node‐positive patients, with a difference in DMFS of 12%. In multivariate analysis, CAB risk score was the most significant predictor of distant recurrence with hazard ratio of 3.2048 (P < 0.0001). CAB stratified patients into discrete risk categories with high statistical significance compared to Ki‐67 and IHC4 score‐based stratification. CAB stratified a higher percentage of the cohort (82%) as low‐risk than IHC4 score (41.6%) and could re‐stratify >74% of high Ki‐67 and IHC4 score intermediate‐risk zone patients into low‐risk category. Overall the data suggest that CAB can effectively predict risk of distant recurrence with clear dichotomous high‐ or low‐risk categorization. John Wiley and Sons Inc. 2019-03-07 /pmc/articles/PMC6488210/ /pubmed/30848103 http://dx.doi.org/10.1002/cam4.2049 Text en © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Biology
Bakre, Manjiri M.
Ramkumar, Charusheila
Attuluri, Arun Kumar
Basavaraj, Chetana
Prakash, Chandra
Buturovic, Ljubomir
Madhav, Lekshmi
Naidu, Nirupama
R, Prathima
Somashekhar, S. P.
Gupta, Sudeep
Doval, Dinesh Chandra
Pegram, Mark D.
Clinical validation of an immunohistochemistry‐based CanAssist‐Breast test for distant recurrence prediction in hormone receptor‐positive breast cancer patients
title Clinical validation of an immunohistochemistry‐based CanAssist‐Breast test for distant recurrence prediction in hormone receptor‐positive breast cancer patients
title_full Clinical validation of an immunohistochemistry‐based CanAssist‐Breast test for distant recurrence prediction in hormone receptor‐positive breast cancer patients
title_fullStr Clinical validation of an immunohistochemistry‐based CanAssist‐Breast test for distant recurrence prediction in hormone receptor‐positive breast cancer patients
title_full_unstemmed Clinical validation of an immunohistochemistry‐based CanAssist‐Breast test for distant recurrence prediction in hormone receptor‐positive breast cancer patients
title_short Clinical validation of an immunohistochemistry‐based CanAssist‐Breast test for distant recurrence prediction in hormone receptor‐positive breast cancer patients
title_sort clinical validation of an immunohistochemistry‐based canassist‐breast test for distant recurrence prediction in hormone receptor‐positive breast cancer patients
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488210/
https://www.ncbi.nlm.nih.gov/pubmed/30848103
http://dx.doi.org/10.1002/cam4.2049
work_keys_str_mv AT bakremanjirim clinicalvalidationofanimmunohistochemistrybasedcanassistbreasttestfordistantrecurrencepredictioninhormonereceptorpositivebreastcancerpatients
AT ramkumarcharusheila clinicalvalidationofanimmunohistochemistrybasedcanassistbreasttestfordistantrecurrencepredictioninhormonereceptorpositivebreastcancerpatients
AT attuluriarunkumar clinicalvalidationofanimmunohistochemistrybasedcanassistbreasttestfordistantrecurrencepredictioninhormonereceptorpositivebreastcancerpatients
AT basavarajchetana clinicalvalidationofanimmunohistochemistrybasedcanassistbreasttestfordistantrecurrencepredictioninhormonereceptorpositivebreastcancerpatients
AT prakashchandra clinicalvalidationofanimmunohistochemistrybasedcanassistbreasttestfordistantrecurrencepredictioninhormonereceptorpositivebreastcancerpatients
AT buturovicljubomir clinicalvalidationofanimmunohistochemistrybasedcanassistbreasttestfordistantrecurrencepredictioninhormonereceptorpositivebreastcancerpatients
AT madhavlekshmi clinicalvalidationofanimmunohistochemistrybasedcanassistbreasttestfordistantrecurrencepredictioninhormonereceptorpositivebreastcancerpatients
AT naidunirupama clinicalvalidationofanimmunohistochemistrybasedcanassistbreasttestfordistantrecurrencepredictioninhormonereceptorpositivebreastcancerpatients
AT rprathima clinicalvalidationofanimmunohistochemistrybasedcanassistbreasttestfordistantrecurrencepredictioninhormonereceptorpositivebreastcancerpatients
AT somashekharsp clinicalvalidationofanimmunohistochemistrybasedcanassistbreasttestfordistantrecurrencepredictioninhormonereceptorpositivebreastcancerpatients
AT guptasudeep clinicalvalidationofanimmunohistochemistrybasedcanassistbreasttestfordistantrecurrencepredictioninhormonereceptorpositivebreastcancerpatients
AT dovaldineshchandra clinicalvalidationofanimmunohistochemistrybasedcanassistbreasttestfordistantrecurrencepredictioninhormonereceptorpositivebreastcancerpatients
AT pegrammarkd clinicalvalidationofanimmunohistochemistrybasedcanassistbreasttestfordistantrecurrencepredictioninhormonereceptorpositivebreastcancerpatients