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Erythropoietin Receptor Expression and Correlation to Tamoxifen Response and Prognosis in Breast Cancer.

Larsson, Anna-Maria LU ; Jirström, Karin LU ; Fredlund, Erik LU ; Björner, Sofie LU ; Rydén, Lisa LU ; Landberg, Göran LU and Påhlman, Sven LU (2009) In Clinical Cancer Research 15(17). p.5552-5559
Abstract
PURPOSE: The main function of erythropoietin (EPO) is to stimulate erythropoiesis. EPO receptors (EPOR) are expressed in other cell types, including tumor cells, suggesting that the EPO/EPOR pathway governs additional cellular processes besides erythropoiesis. Recombinant EPO (rhEPO) is frequently given to anemic cancer patients, although data on clinical outcome are conflicting. In an attempt to understand these clinical data, we analyzed EPO and EPOR expression in breast cancer and evaluated EPOR as a putative prognostic and predictive marker in breast cancer patients treated with tamoxifen. EXPERIMENTAL DESIGN: EPO mRNA/protein and EPOR mRNA were quantified by PCR and ELISA, respectively. Tissue microarrays containing 500 breast tumors... (More)
PURPOSE: The main function of erythropoietin (EPO) is to stimulate erythropoiesis. EPO receptors (EPOR) are expressed in other cell types, including tumor cells, suggesting that the EPO/EPOR pathway governs additional cellular processes besides erythropoiesis. Recombinant EPO (rhEPO) is frequently given to anemic cancer patients, although data on clinical outcome are conflicting. In an attempt to understand these clinical data, we analyzed EPO and EPOR expression in breast cancer and evaluated EPOR as a putative prognostic and predictive marker in breast cancer patients treated with tamoxifen. EXPERIMENTAL DESIGN: EPO mRNA/protein and EPOR mRNA were quantified by PCR and ELISA, respectively. Tissue microarrays containing 500 breast tumors from premenopausal women randomized to tamoxifen or no adjuvant treatment were evaluated for EPOR expression by immunohistochemistry. Predictive and prognostic information was evaluated using Kaplan-Meier curves and log-rank tests to estimate recurrence-free survival (RFS). RESULTS: EPO and EPOR were expressed in cultured cells, and breast tumor specimens expressed EPOR at varying levels. Tamoxifen treatment significantly increased RFS in patients with estrogen receptor-positive/progesterone receptor-positive (ER(+)/PR(+)) tumors with low EPOR expression (P = 0.001) but had no effect on RFS in patients with tumors with high EPOR expression (P = 0.98). In the untreated cohort, RFS was significantly improved for patients with ER(+) tumors with high EPOR expression. CONCLUSION: EPOR is abundantly expressed in breast cancer specimens. The fact that high expression of EPOR is related to an impaired tamoxifen response in ER(+)/PR(+) tumors and to improved survival in untreated patients suggests that EPOR expression in breast cancer affects tumor behavior. (Clin Cancer Res 2009;15(17):5552-9). (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Cancer Research
volume
15
issue
17
pages
5552 - 5559
publisher
American Association for Cancer Research
external identifiers
  • wos:000269565800032
  • pmid:19706814
  • scopus:69949089786
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-08-3014
project
CREATE Health
language
English
LU publication?
yes
id
17e57a59-b2ee-43d8-956f-16b03bcb9442 (old id 1469363)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19706814?dopt=Abstract
date added to LUP
2009-09-07 15:37:38
date last changed
2017-07-23 04:53:34
@article{17e57a59-b2ee-43d8-956f-16b03bcb9442,
  abstract     = {PURPOSE: The main function of erythropoietin (EPO) is to stimulate erythropoiesis. EPO receptors (EPOR) are expressed in other cell types, including tumor cells, suggesting that the EPO/EPOR pathway governs additional cellular processes besides erythropoiesis. Recombinant EPO (rhEPO) is frequently given to anemic cancer patients, although data on clinical outcome are conflicting. In an attempt to understand these clinical data, we analyzed EPO and EPOR expression in breast cancer and evaluated EPOR as a putative prognostic and predictive marker in breast cancer patients treated with tamoxifen. EXPERIMENTAL DESIGN: EPO mRNA/protein and EPOR mRNA were quantified by PCR and ELISA, respectively. Tissue microarrays containing 500 breast tumors from premenopausal women randomized to tamoxifen or no adjuvant treatment were evaluated for EPOR expression by immunohistochemistry. Predictive and prognostic information was evaluated using Kaplan-Meier curves and log-rank tests to estimate recurrence-free survival (RFS). RESULTS: EPO and EPOR were expressed in cultured cells, and breast tumor specimens expressed EPOR at varying levels. Tamoxifen treatment significantly increased RFS in patients with estrogen receptor-positive/progesterone receptor-positive (ER(+)/PR(+)) tumors with low EPOR expression (P = 0.001) but had no effect on RFS in patients with tumors with high EPOR expression (P = 0.98). In the untreated cohort, RFS was significantly improved for patients with ER(+) tumors with high EPOR expression. CONCLUSION: EPOR is abundantly expressed in breast cancer specimens. The fact that high expression of EPOR is related to an impaired tamoxifen response in ER(+)/PR(+) tumors and to improved survival in untreated patients suggests that EPOR expression in breast cancer affects tumor behavior. (Clin Cancer Res 2009;15(17):5552-9).},
  author       = {Larsson, Anna-Maria and Jirström, Karin and Fredlund, Erik and Björner, Sofie and Rydén, Lisa and Landberg, Göran and Påhlman, Sven},
  issn         = {1078-0432},
  language     = {eng},
  number       = {17},
  pages        = {5552--5559},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {Erythropoietin Receptor Expression and Correlation to Tamoxifen Response and Prognosis in Breast Cancer.},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-08-3014},
  volume       = {15},
  year         = {2009},
}