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Global microRNA expression profiling of high-risk ER+ breast cancers from patients receiving adjuvant tamoxifen mono-therapy : a DBCG study

Lyng, Maria B; Lænkholm, Anne-Vibeke; Søkilde, Rolf LU ; Gravgaard, Karina H; Litman, Thomas and Ditzel, Henrik J (2012) In PLoS ONE 7(5).
Abstract

PURPOSE: Despite the benefits of estrogen receptor (ER)-targeted endocrine therapies in breast cancer, many tumors develop resistance. MicroRNAs (miRNAs) have been suggested as promising biomarkers and we here evaluated whether a miRNA profile could be identified, sub-grouping ER+ breast cancer patients treated with adjuvant Tamoxifen with regards to probability of recurrence.

EXPERIMENTAL DESIGN: Global miRNA analysis was performed on 152 ER+ primary tumors from high-risk breast cancer patients with an initial discovery set of 52 patients, followed by two independent test sets (N = 60 and N = 40). All patients had received adjuvant Tamoxifen as mono-therapy (median clinical follow-up: 4.6 years) and half had developed distant... (More)

PURPOSE: Despite the benefits of estrogen receptor (ER)-targeted endocrine therapies in breast cancer, many tumors develop resistance. MicroRNAs (miRNAs) have been suggested as promising biomarkers and we here evaluated whether a miRNA profile could be identified, sub-grouping ER+ breast cancer patients treated with adjuvant Tamoxifen with regards to probability of recurrence.

EXPERIMENTAL DESIGN: Global miRNA analysis was performed on 152 ER+ primary tumors from high-risk breast cancer patients with an initial discovery set of 52 patients, followed by two independent test sets (N = 60 and N = 40). All patients had received adjuvant Tamoxifen as mono-therapy (median clinical follow-up: 4.6 years) and half had developed distant recurrence (median time-to-recurrence: 3.5 years). MiRNA expression was examined by unsupervised hierarchical clustering and supervised analysis, including clinical parameters as co-variables.

RESULTS: The discovery set identified 10 highly significant miRNAs that discriminated between the patient samples according to outcome. However, the subsequent two independent test sets did not confirm the predictive potential of these miRNAs. A significant correlation was identified between miR-7 and the tumor grade. Investigation of the microRNAs with the most variable expression between patients in different runs yielded a list of 31 microRNAs, eight of which are associated with stem cell characteristics.

CONCLUSIONS: Based on the large sample size, our data strongly suggests that there is no single miRNA profile predictive of outcome following adjuvant Tamoxifen treatment in a broad cohort of ER+ breast cancer patients. We identified a sub-group of Tamoxifen-treated breast cancer patients with miRNA-expressing tumors associated with cancer stem cell characteristics.

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published
keywords
Antineoplastic Agents, Hormonal, Breast Neoplasms, Cluster Analysis, Female, Gene Expression Profiling, Humans, MicroRNAs, Receptors, Estrogen, Tamoxifen, Journal Article, Research Support, Non-U.S. Gov't
in
PLoS ONE
volume
7
issue
5
publisher
Public Library of Science
external identifiers
  • scopus:84862109179
ISSN
1932-6203
DOI
10.1371/journal.pone.0036170
language
English
LU publication?
no
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6355feff-37bf-4996-8520-7d55dbf1b67b
date added to LUP
2017-09-01 14:29:23
date last changed
2017-09-08 14:31:35
@article{6355feff-37bf-4996-8520-7d55dbf1b67b,
  abstract     = {<p>PURPOSE: Despite the benefits of estrogen receptor (ER)-targeted endocrine therapies in breast cancer, many tumors develop resistance. MicroRNAs (miRNAs) have been suggested as promising biomarkers and we here evaluated whether a miRNA profile could be identified, sub-grouping ER+ breast cancer patients treated with adjuvant Tamoxifen with regards to probability of recurrence.</p><p>EXPERIMENTAL DESIGN: Global miRNA analysis was performed on 152 ER+ primary tumors from high-risk breast cancer patients with an initial discovery set of 52 patients, followed by two independent test sets (N = 60 and N = 40). All patients had received adjuvant Tamoxifen as mono-therapy (median clinical follow-up: 4.6 years) and half had developed distant recurrence (median time-to-recurrence: 3.5 years). MiRNA expression was examined by unsupervised hierarchical clustering and supervised analysis, including clinical parameters as co-variables.</p><p>RESULTS: The discovery set identified 10 highly significant miRNAs that discriminated between the patient samples according to outcome. However, the subsequent two independent test sets did not confirm the predictive potential of these miRNAs. A significant correlation was identified between miR-7 and the tumor grade. Investigation of the microRNAs with the most variable expression between patients in different runs yielded a list of 31 microRNAs, eight of which are associated with stem cell characteristics.</p><p>CONCLUSIONS: Based on the large sample size, our data strongly suggests that there is no single miRNA profile predictive of outcome following adjuvant Tamoxifen treatment in a broad cohort of ER+ breast cancer patients. We identified a sub-group of Tamoxifen-treated breast cancer patients with miRNA-expressing tumors associated with cancer stem cell characteristics.</p>},
  articleno    = {e36170},
  author       = {Lyng, Maria B and Lænkholm, Anne-Vibeke and Søkilde, Rolf and Gravgaard, Karina H and Litman, Thomas and Ditzel, Henrik J},
  issn         = {1932-6203},
  keyword      = {Antineoplastic Agents, Hormonal,Breast Neoplasms,Cluster Analysis,Female,Gene Expression Profiling,Humans,MicroRNAs,Receptors, Estrogen,Tamoxifen,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {5},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Global microRNA expression profiling of high-risk ER+ breast cancers from patients receiving adjuvant tamoxifen mono-therapy : a DBCG study},
  url          = {http://dx.doi.org/10.1371/journal.pone.0036170},
  volume       = {7},
  year         = {2012},
}