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Contrasting breast cancer molecular subtypes across serial tumor progression stages: biological and prognostic implications.

Kimbung, Siker LU ; Kovács, Anikó; Danielsson, Anna; Bendahl, Pär-Ola LU ; Lövgren, Kristina LU ; Stolt, Marianne Frostvik; Tobin, Nicholas P; Lindström, Linda; Bergh, Jonas and Einbeigi, Zakaria, et al. (2015) In Oncotarget 6(32). p.33306-33318
Abstract
The relevance of the intrinsic subtypes for clinical management of metastatic breast cancer is not comprehensively established. We aimed to evaluate the prevalence and prognostic significance of drifts in tumor molecular subtypes during breast cancer progression. A well-annotated cohort of 304 women with advanced breast cancer was studied. Tissue microarrays of primary tumors and synchronous lymph node metastases were constructed. Conventional biomarkers were centrally assessed and molecular subtypes were assigned following the 2013 St Gallen guidelines. Fine-needle aspirates of asynchronous metastases were transcriptionally profiled and subtyped using PAM50. Discordant expression of individual biomarkers and molecular subtypes was... (More)
The relevance of the intrinsic subtypes for clinical management of metastatic breast cancer is not comprehensively established. We aimed to evaluate the prevalence and prognostic significance of drifts in tumor molecular subtypes during breast cancer progression. A well-annotated cohort of 304 women with advanced breast cancer was studied. Tissue microarrays of primary tumors and synchronous lymph node metastases were constructed. Conventional biomarkers were centrally assessed and molecular subtypes were assigned following the 2013 St Gallen guidelines. Fine-needle aspirates of asynchronous metastases were transcriptionally profiled and subtyped using PAM50. Discordant expression of individual biomarkers and molecular subtypes was observed during tumor progression. Primary luminal-like tumors were relatively unstable, frequently adopting a more aggressive subtype in the metastases. Notably, loss of ER expression and a luminal to non-luminal subtype conversion was associated with an inferior post-recurrence survival. In addition, ER and molecular subtype assessed at all tumor progression stages were independent prognostic factors for post-recurrence breast cancer mortality in multivariable analyses. Our results demonstrate that drifts in tumor molecular subtypes may occur during tumor progression, conferring adverse consequences on outcome following breast cancer relapse. (Less)
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Contribution to journal
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published
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Oncotarget
volume
6
issue
32
pages
33306 - 33318
publisher
Impact Journals, LLC
external identifiers
  • pmid:26375671
  • wos:000363186600091
  • scopus:84946025828
ISSN
1949-2553
DOI
10.18632/oncotarget.5089
language
English
LU publication?
yes
id
76ea4f20-b596-4aca-8d3b-15f4a6c4e907 (old id 8039009)
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http://www.ncbi.nlm.nih.gov/pubmed/26375671?dopt=Abstract
date added to LUP
2015-10-03 21:00:30
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2017-08-13 03:49:27
@article{76ea4f20-b596-4aca-8d3b-15f4a6c4e907,
  abstract     = {The relevance of the intrinsic subtypes for clinical management of metastatic breast cancer is not comprehensively established. We aimed to evaluate the prevalence and prognostic significance of drifts in tumor molecular subtypes during breast cancer progression. A well-annotated cohort of 304 women with advanced breast cancer was studied. Tissue microarrays of primary tumors and synchronous lymph node metastases were constructed. Conventional biomarkers were centrally assessed and molecular subtypes were assigned following the 2013 St Gallen guidelines. Fine-needle aspirates of asynchronous metastases were transcriptionally profiled and subtyped using PAM50. Discordant expression of individual biomarkers and molecular subtypes was observed during tumor progression. Primary luminal-like tumors were relatively unstable, frequently adopting a more aggressive subtype in the metastases. Notably, loss of ER expression and a luminal to non-luminal subtype conversion was associated with an inferior post-recurrence survival. In addition, ER and molecular subtype assessed at all tumor progression stages were independent prognostic factors for post-recurrence breast cancer mortality in multivariable analyses. Our results demonstrate that drifts in tumor molecular subtypes may occur during tumor progression, conferring adverse consequences on outcome following breast cancer relapse.},
  author       = {Kimbung, Siker and Kovács, Anikó and Danielsson, Anna and Bendahl, Pär-Ola and Lövgren, Kristina and Stolt, Marianne Frostvik and Tobin, Nicholas P and Lindström, Linda and Bergh, Jonas and Einbeigi, Zakaria and Fernö, Mårten and Hatschek, Thomas and Hedenfalk, Ingrid},
  issn         = {1949-2553},
  language     = {eng},
  number       = {32},
  pages        = {33306--33318},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Contrasting breast cancer molecular subtypes across serial tumor progression stages: biological and prognostic implications.},
  url          = {http://dx.doi.org/10.18632/oncotarget.5089},
  volume       = {6},
  year         = {2015},
}