Journal
ONCOTARGET
Volume 6, Issue 32, Pages 33306-33318Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.5089
Keywords
metastatic breast cancer; estrogen receptor; molecular subtype; biomarker conversion; post recurrence mortality
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Funding
- Swedish Cancer Society
- Swedish Research Council
- Gunnar Nilsson Cancer Foundation
- Berta Kamprad Foundation
- Gyllenstierna Krapperup's Foundation
- Swedish Cancer and Allergy Foundation
- Research Funds at Radiumhemmet
- Swedish Breast Cancer Association (BRO)
- ALF/FOU research funds at the Karolinska Institutet
- Stockholm County Council
- Bristol-Myers Squibb Sweden AB
- Pfizer Sweden AB
- Roche Sweden AB
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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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