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...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2019 |
| Country: | España |
| Institution: | INCLIVA |
| Repository: | r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| OAI Identifier: | oai:incliva.fundanetsuite.com:p3642 |
| Online Access: | https://incliva.portalinvestigacion.com/publicaciones/3642 |
| Access Level: | Open access |
| Keyword: | intrinsic subtype non-luminal PAM50 breast cancer gene expression |
| _version_ | 1878735600991862784 |
|---|---|
| author | Pascual, T |
| 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 |
| author_browse | Adamo, B Alba, E Cejalvo, JM Chic, N Cortes, J Fernandez-Martinez, A Galvan, P Gonzalez-Farre, B Jares, P Lluch, A Martin, M Morales, S Munoz, M Pare, L Pascual, T Perrone, G Prat, A Righi, D Rodriguez, A Rodriguez-Lescure, A Tonini, G Urruticoechea, A Vidal, M Villagrasa, P |
| 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 |
| collection | r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_7ff286c4e0f2fa4f6b3317022669c220 |
| institution | INCLIVA |
| instname_str | INCLIVA |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:incliva.fundanetsuite.com:p3642 |
| publishDate | 2019 |
| publishDateSort | 2019 |
| publisher | FRONTIERS MEDIA SA |
| publisherStr | FRONTIERS MEDIA SA |
| reponame_str | r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| spelling | A Pathology-Based Combined Model to Identify PAM50 Non-luminal Intrinsic Disease in Hormone Receptor-Positive HER2-Negative Breast Cancer 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 intrinsic subtype non-luminal PAM50 breast cancer gene expression 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. FRONTIERS MEDIA SA https://incliva.portalinvestigacion.com/publicaciones/3642 |
| 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 |
| status_str | publishedVersion |
| title | 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_short | 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 |
| topic | intrinsic subtype non-luminal PAM50 breast cancer gene expression |
| topic_facet | intrinsic subtype non-luminal PAM50 breast cancer gene expression |
| url | https://incliva.portalinvestigacion.com/publicaciones/3642 |