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

Journal article
Authors Siker Kimbung
Anikó Kovács
Anna Danielsson
Pär-Ola Bendahl
Kristina Lövgren
Marianne Frostvik Stolt
Nicholas P Tobin
Linda Lindström
Jonas Bergh
Zakaria Einbeigi
Mårten Fernö
Thomas Hatschek
Ingrid Hedenfalk
Published in Oncotarget
Volume 6
Issue 32
Pages 33306-18
ISSN 1949-2553
Publication year 2015
Published at Institute of Clinical Sciences, Department of Oncology
Pages 33306-18
Language en
Subject categories Cancer and Oncology


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.

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