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BluePrint breast cancer molecular subtyping recognizes single and dual subtype tumors with implications for therapeutic guidance
PURPOSE: BluePrint (BP) is an 80-gene molecular subtyping test that classifies early-stage breast cancer (EBC) into Basal, Luminal, and HER2 subtypes. In most cases, breast tumors have one dominant subtype, representative of a single activated pathway. However, some tumors show a statistically equal...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464757/ https://www.ncbi.nlm.nih.gov/pubmed/35984580 http://dx.doi.org/10.1007/s10549-022-06698-x |
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author | Kuilman, Midas M. Ellappalayam, Architha Barcaru, Andrei Haan, Josien C. Bhaskaran, Rajith Wehkamp, Diederik Menicucci, Andrea R. Audeh, William M. Mittempergher, Lorenza Glas, Annuska M. |
author_facet | Kuilman, Midas M. Ellappalayam, Architha Barcaru, Andrei Haan, Josien C. Bhaskaran, Rajith Wehkamp, Diederik Menicucci, Andrea R. Audeh, William M. Mittempergher, Lorenza Glas, Annuska M. |
author_sort | Kuilman, Midas M. |
collection | PubMed |
description | PURPOSE: BluePrint (BP) is an 80-gene molecular subtyping test that classifies early-stage breast cancer (EBC) into Basal, Luminal, and HER2 subtypes. In most cases, breast tumors have one dominant subtype, representative of a single activated pathway. However, some tumors show a statistically equal representation of more than one subtype, referred to as dual subtype. This study aims to identify and examine dual subtype tumors by BP to understand their biology and possible implications for treatment guidance. METHODS: The BP scores of over 15,000 tumor samples from EBC patients were analyzed, and the differences between the highest and the lowest scoring subtypes were calculated. Based upon the distribution of the differences between BP scores, a threshold was determined for each subtype to identify dual versus single subtypes. RESULTS: Approximately 97% of samples had one single activated BluePrint molecular subtype, whereas ~ 3% of samples were classified as BP dual subtype. The most frequently occurring dual subtypes were the Luminal-Basal-type and Luminal-HER2-type. Luminal-Basal-type displays a distinct biology from the Luminal single type and Basal single type. Burstein’s classification of the single and dual Basal samples showed that the Luminal-Basal-type is mostly classified as ‘luminal androgen receptor’ and ‘mesenchymal’ subtypes, supporting molecular evidence of AR activation in the Luminal-Basal-type tumors. Tumors classified as Luminal-HER2-type resemble features of both Luminal-single-type and HER2-single-type. However, patients with dual Luminal-HER2-type have a lower pathological complete response after receiving HER2-targeted therapies in addition to chemotherapy in comparison with patients with a HER2-single-type. CONCLUSION: This study demonstrates that BP identifies tumors with two active functional pathways (dual subtype) with specific transcriptional characteristics and highlights the added value of distinguishing BP dual from single subtypes as evidenced by distinct treatment response rates. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10549-022-06698-x. |
format | Online Article Text |
id | pubmed-9464757 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-94647572022-09-13 BluePrint breast cancer molecular subtyping recognizes single and dual subtype tumors with implications for therapeutic guidance Kuilman, Midas M. Ellappalayam, Architha Barcaru, Andrei Haan, Josien C. Bhaskaran, Rajith Wehkamp, Diederik Menicucci, Andrea R. Audeh, William M. Mittempergher, Lorenza Glas, Annuska M. Breast Cancer Res Treat Preclinical Study PURPOSE: BluePrint (BP) is an 80-gene molecular subtyping test that classifies early-stage breast cancer (EBC) into Basal, Luminal, and HER2 subtypes. In most cases, breast tumors have one dominant subtype, representative of a single activated pathway. However, some tumors show a statistically equal representation of more than one subtype, referred to as dual subtype. This study aims to identify and examine dual subtype tumors by BP to understand their biology and possible implications for treatment guidance. METHODS: The BP scores of over 15,000 tumor samples from EBC patients were analyzed, and the differences between the highest and the lowest scoring subtypes were calculated. Based upon the distribution of the differences between BP scores, a threshold was determined for each subtype to identify dual versus single subtypes. RESULTS: Approximately 97% of samples had one single activated BluePrint molecular subtype, whereas ~ 3% of samples were classified as BP dual subtype. The most frequently occurring dual subtypes were the Luminal-Basal-type and Luminal-HER2-type. Luminal-Basal-type displays a distinct biology from the Luminal single type and Basal single type. Burstein’s classification of the single and dual Basal samples showed that the Luminal-Basal-type is mostly classified as ‘luminal androgen receptor’ and ‘mesenchymal’ subtypes, supporting molecular evidence of AR activation in the Luminal-Basal-type tumors. Tumors classified as Luminal-HER2-type resemble features of both Luminal-single-type and HER2-single-type. However, patients with dual Luminal-HER2-type have a lower pathological complete response after receiving HER2-targeted therapies in addition to chemotherapy in comparison with patients with a HER2-single-type. CONCLUSION: This study demonstrates that BP identifies tumors with two active functional pathways (dual subtype) with specific transcriptional characteristics and highlights the added value of distinguishing BP dual from single subtypes as evidenced by distinct treatment response rates. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10549-022-06698-x. Springer US 2022-08-19 2022 /pmc/articles/PMC9464757/ /pubmed/35984580 http://dx.doi.org/10.1007/s10549-022-06698-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Preclinical Study Kuilman, Midas M. Ellappalayam, Architha Barcaru, Andrei Haan, Josien C. Bhaskaran, Rajith Wehkamp, Diederik Menicucci, Andrea R. Audeh, William M. Mittempergher, Lorenza Glas, Annuska M. BluePrint breast cancer molecular subtyping recognizes single and dual subtype tumors with implications for therapeutic guidance |
title | BluePrint breast cancer molecular subtyping recognizes single and dual subtype tumors with implications for therapeutic guidance |
title_full | BluePrint breast cancer molecular subtyping recognizes single and dual subtype tumors with implications for therapeutic guidance |
title_fullStr | BluePrint breast cancer molecular subtyping recognizes single and dual subtype tumors with implications for therapeutic guidance |
title_full_unstemmed | BluePrint breast cancer molecular subtyping recognizes single and dual subtype tumors with implications for therapeutic guidance |
title_short | BluePrint breast cancer molecular subtyping recognizes single and dual subtype tumors with implications for therapeutic guidance |
title_sort | blueprint breast cancer molecular subtyping recognizes single and dual subtype tumors with implications for therapeutic guidance |
topic | Preclinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464757/ https://www.ncbi.nlm.nih.gov/pubmed/35984580 http://dx.doi.org/10.1007/s10549-022-06698-x |
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