A Pathology-Based Combined Model to Identify PAM50 Non-luminal Intrinsic Disease in Hormone Receptor-Positive HER2-Negative Breast Cancer

Background: In hormone receptor-positive (HR+)/HER2-negative breast cancer, the HER2-enriched and Basal-like intrinsic subtypes are associated with poor outcome, low response to anti-estrogen therapy and high response to chemotherapy. To date, no validated biomarker exists to identify both molecular...

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Autores: Pascual, T, Martin, M, Fernandez-Martinez, A, Pare, L, Alba, E, Rodriguez-Lescure, A, Perrone, G, Cortes, J, Morales, S, Lluch, A, Urruticoechea, A, Gonzalez-Farre, B, Galvan, P, Jares, P, Rodriguez, A, Chic, N, Righi, D, Cejalvo, JM, Tonini, G, Adamo, B, Vidal, M, Villagrasa, P, Munoz, M, Prat, A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p3642
Acceso en línea:https://incliva.portalinvestigacion.com/publicaciones/3642
Access Level:acceso abierto
Palabra clave:intrinsic subtype
non-luminal
PAM50
breast cancer
gene expression
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spelling A Pathology-Based Combined Model to Identify PAM50 Non-luminal Intrinsic Disease in Hormone Receptor-Positive HER2-Negative Breast CancerPascual, TMartin, MFernandez-Martinez, APare, LAlba, ERodriguez-Lescure, APerrone, GCortes, JMorales, SLluch, AUrruticoechea, AGonzalez-Farre, BGalvan, PJares, PRodriguez, AChic, NRighi, DCejalvo, JMTonini, GAdamo, BVidal, MVillagrasa, PMunoz, MPrat, Aintrinsic subtypenon-luminalPAM50breast cancergene expressionBackground: In hormone receptor-positive (HR+)/HER2-negative breast cancer, the HER2-enriched and Basal-like intrinsic subtypes are associated with poor outcome, low response to anti-estrogen therapy and high response to chemotherapy. To date, no validated biomarker exists to identify both molecular entities other than gene expression. Methods: PAM50 subtyping and immunohistochemical data were obtained from 8 independent studies of 1,416 HR+/HER2-negative early breast tumors. A non-luminal disease score (NOLUS) from 0 to 100, based on percentage of estrogen receptor (ER), progesterone receptor (PR) and Ki67 tumor cells, was derived in a combined cohort of 5 studies (training dataset) and tested in a combined cohort of 3 studies. The performance of NOLUS was estimated using Area Under the ROC Curve (AUC). Results: In the training dataset (n = 903) and compared to luminal disease, non-luminal disease had lower percentage of ER-positive cells (median 65.2 vs. 86.2%, p < 0.01) and PR-positive cells (33.2 vs. 56.4%, p < 0.01) and higher percentage of Ki67-positive cells (18.2 vs. 13.1%, p = 0.01). A NOLUS formula was derived: -0.45*ER -0.28*PR +0.27*Ki67 + 73.02. The proportion of non-luminal tumors in NOLUS-positive (>= 51.38) and NOLUS-negative (<51.38) groups was 52.6 and 8.7%, respectively. In the testing dataset (n = 514), NOLUS was found significantly associated with non-luminal disease (p < 0.01) with an AUC 0.902. The proportion of non-luminal tumors in NOLUS-positive and NOLUS-negative groups was 76.9% (56.4-91.0%) and 2.6% (1.4-4.5%), respectively. The sensitivity and specificity of the pre-specified cutoff was 59.3 and 98.7%, respectively. Conclusions: In the absence of gene expression data, NOLUS can help identify non-luminal disease within HR+/HER2-negative breast cancer.FRONTIERS MEDIA SA2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/3642Frontiers in OncologyISSN: 2234943Xreponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p36422026-06-07T16:35:31Z
dc.title.none.fl_str_mv A Pathology-Based Combined Model to Identify PAM50 Non-luminal Intrinsic Disease in Hormone Receptor-Positive HER2-Negative Breast Cancer
title A Pathology-Based Combined Model to Identify PAM50 Non-luminal Intrinsic Disease in Hormone Receptor-Positive HER2-Negative Breast Cancer
spellingShingle A Pathology-Based Combined Model to Identify PAM50 Non-luminal Intrinsic Disease in Hormone Receptor-Positive HER2-Negative Breast Cancer
Pascual, T
intrinsic subtype
non-luminal
PAM50
breast cancer
gene expression
title_short A Pathology-Based Combined Model to Identify PAM50 Non-luminal Intrinsic Disease in Hormone Receptor-Positive HER2-Negative Breast Cancer
title_full A Pathology-Based Combined Model to Identify PAM50 Non-luminal Intrinsic Disease in Hormone Receptor-Positive HER2-Negative Breast Cancer
title_fullStr A Pathology-Based Combined Model to Identify PAM50 Non-luminal Intrinsic Disease in Hormone Receptor-Positive HER2-Negative Breast Cancer
title_full_unstemmed A Pathology-Based Combined Model to Identify PAM50 Non-luminal Intrinsic Disease in Hormone Receptor-Positive HER2-Negative Breast Cancer
title_sort A Pathology-Based Combined Model to Identify PAM50 Non-luminal Intrinsic Disease in Hormone Receptor-Positive HER2-Negative Breast Cancer
dc.creator.none.fl_str_mv Pascual, T
Martin, M
Fernandez-Martinez, A
Pare, L
Alba, E
Rodriguez-Lescure, A
Perrone, G
Cortes, J
Morales, S
Lluch, A
Urruticoechea, A
Gonzalez-Farre, B
Galvan, P
Jares, P
Rodriguez, A
Chic, N
Righi, D
Cejalvo, JM
Tonini, G
Adamo, B
Vidal, M
Villagrasa, P
Munoz, M
Prat, A
author Pascual, T
author_facet Pascual, T
Martin, M
Fernandez-Martinez, A
Pare, L
Alba, E
Rodriguez-Lescure, A
Perrone, G
Cortes, J
Morales, S
Lluch, A
Urruticoechea, A
Gonzalez-Farre, B
Galvan, P
Jares, P
Rodriguez, A
Chic, N
Righi, D
Cejalvo, JM
Tonini, G
Adamo, B
Vidal, M
Villagrasa, P
Munoz, M
Prat, A
author_role author
author2 Martin, M
Fernandez-Martinez, A
Pare, L
Alba, E
Rodriguez-Lescure, A
Perrone, G
Cortes, J
Morales, S
Lluch, A
Urruticoechea, A
Gonzalez-Farre, B
Galvan, P
Jares, P
Rodriguez, A
Chic, N
Righi, D
Cejalvo, JM
Tonini, G
Adamo, B
Vidal, M
Villagrasa, P
Munoz, M
Prat, A
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv intrinsic subtype
non-luminal
PAM50
breast cancer
gene expression
topic intrinsic subtype
non-luminal
PAM50
breast cancer
gene expression
description Background: In hormone receptor-positive (HR+)/HER2-negative breast cancer, the HER2-enriched and Basal-like intrinsic subtypes are associated with poor outcome, low response to anti-estrogen therapy and high response to chemotherapy. To date, no validated biomarker exists to identify both molecular entities other than gene expression. Methods: PAM50 subtyping and immunohistochemical data were obtained from 8 independent studies of 1,416 HR+/HER2-negative early breast tumors. A non-luminal disease score (NOLUS) from 0 to 100, based on percentage of estrogen receptor (ER), progesterone receptor (PR) and Ki67 tumor cells, was derived in a combined cohort of 5 studies (training dataset) and tested in a combined cohort of 3 studies. The performance of NOLUS was estimated using Area Under the ROC Curve (AUC). Results: In the training dataset (n = 903) and compared to luminal disease, non-luminal disease had lower percentage of ER-positive cells (median 65.2 vs. 86.2%, p < 0.01) and PR-positive cells (33.2 vs. 56.4%, p < 0.01) and higher percentage of Ki67-positive cells (18.2 vs. 13.1%, p = 0.01). A NOLUS formula was derived: -0.45*ER -0.28*PR +0.27*Ki67 + 73.02. The proportion of non-luminal tumors in NOLUS-positive (>= 51.38) and NOLUS-negative (<51.38) groups was 52.6 and 8.7%, respectively. In the testing dataset (n = 514), NOLUS was found significantly associated with non-luminal disease (p < 0.01) with an AUC 0.902. The proportion of non-luminal tumors in NOLUS-positive and NOLUS-negative groups was 76.9% (56.4-91.0%) and 2.6% (1.4-4.5%), respectively. The sensitivity and specificity of the pre-specified cutoff was 59.3 and 98.7%, respectively. Conclusions: In the absence of gene expression data, NOLUS can help identify non-luminal disease within HR+/HER2-negative breast cancer.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://incliva.portalinvestigacion.com/publicaciones/3642
url https://incliva.portalinvestigacion.com/publicaciones/3642
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv FRONTIERS MEDIA SA
publisher.none.fl_str_mv FRONTIERS MEDIA SA
dc.source.none.fl_str_mv Frontiers in Oncology
ISSN: 2234943X
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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