Hypoxia inducible factor-1alpha is a prognostic marker in premenopausal patients with intermediate to highly differentiated breast cancer but not a predictive marker for tamoxifen response.
Kronblad, Åsa LU ; Jirström, Karin LU
; Rydén, Lisa
LU
; Nordenskjold, Bo
and Landberg, Göran
LU
(2006)
In International Journal of Cancer
118(10).
p.2609-2616
- Abstract
- Hypoxia is common in many solid tumours, including breast cancer. Hypoxia triggers the expression of hypoxia inducible factor-1 alpha (HIF-1 alpha), and HIF-1 alpha has been associated with an impaired prognosis in breast cancer and down-regulation of the oestrogen receptor (ER), potentially affecting the treatment efficiency of antioestrogens. The role of HIF-1 alpha regarding prognostic and treatment predictive information in breast cancer has not been established and we therefore analyzed HIF-1 alpha using immunohistochemistry in a cohort of 377 premenopausal stage II breast cancers arranged in a tissue microarray. The patients were included in a randomized trial with either 2 years of tamoxifen or no adjuvant treatment. The tamoxifen... (More)
- Hypoxia is common in many solid tumours, including breast cancer. Hypoxia triggers the expression of hypoxia inducible factor-1 alpha (HIF-1 alpha), and HIF-1 alpha has been associated with an impaired prognosis in breast cancer and down-regulation of the oestrogen receptor (ER), potentially affecting the treatment efficiency of antioestrogens. The role of HIF-1 alpha regarding prognostic and treatment predictive information in breast cancer has not been established and we therefore analyzed HIF-1 alpha using immunohistochemistry in a cohort of 377 premenopausal stage II breast cancers arranged in a tissue microarray. The patients were included in a randomized trial with either 2 years of tamoxifen or no adjuvant treatment. The tamoxifen treatment effect could be studied in subgroups of breast cancer and pure prognostic information could be scrutinized for untreated control patients. HIF-1 alpha was scored as positive in 24% of the tumours and correlated positively to tumour size, Nottingham histological grade (NHG), Ki-67, Her2 and cyclin E expression and negatively to lymph node status, cyclin D1, ER and PR (progesterone receptor) expression. Surprisingly, there was no difference in tamoxifen response for patients with high or low HIF-1 alpha expressing tumours. In lymph node-positive patients as well as NHG 1/2 tumours, high HIF-1 alpha protein expression was significantly associated with an impaired recurrence-free survival (p = 0.014, 0.0.18). When analyzing the subgroup of NHG 1/2 tumours, a high HIF-1 alpha expression was the only independent significant prognostic marker in multivariate analysis, including standard prognostic markers, suggesting that HIF-1a might be a useful prognostic marker in this subgroup of breast cancer, with a rather good but diverse prognosis. (c) 2005 Wiley-Liss, Inc. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/148452
- author
- Kronblad, Åsa
LU
; Jirström, Karin
LU
; Rydén, Lisa
LU
; Nordenskjold, Bo
and Landberg, Göran
LU
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- tamoxifen treatment, prognosis, HIF-1 alpha, breast cancer
- in
- International Journal of Cancer
- volume
- 118
- issue
- 10
- pages
- 2609 - 2616
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:16381002
- wos:000237029200035
- scopus:33646423829
- pmid:16381002
- ISSN
- 0020-7136
- DOI
- 10.1002/ijc.21676
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology (Malmö) (013031000), Oncology, MV (013035000), Surgery (Lund) (013009000), Pathology, (Lund) (013030000)
- id
- 1a7155ce-359d-491c-a332-8fa765041e7a (old id 148452)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16381002&dopt=Abstract
- date added to LUP
- 2016-04-01 11:55:05
- date last changed
- 2024-01-08 01:24:21
@article{1a7155ce-359d-491c-a332-8fa765041e7a,
abstract = {{Hypoxia is common in many solid tumours, including breast cancer. Hypoxia triggers the expression of hypoxia inducible factor-1 alpha (HIF-1 alpha), and HIF-1 alpha has been associated with an impaired prognosis in breast cancer and down-regulation of the oestrogen receptor (ER), potentially affecting the treatment efficiency of antioestrogens. The role of HIF-1 alpha regarding prognostic and treatment predictive information in breast cancer has not been established and we therefore analyzed HIF-1 alpha using immunohistochemistry in a cohort of 377 premenopausal stage II breast cancers arranged in a tissue microarray. The patients were included in a randomized trial with either 2 years of tamoxifen or no adjuvant treatment. The tamoxifen treatment effect could be studied in subgroups of breast cancer and pure prognostic information could be scrutinized for untreated control patients. HIF-1 alpha was scored as positive in 24% of the tumours and correlated positively to tumour size, Nottingham histological grade (NHG), Ki-67, Her2 and cyclin E expression and negatively to lymph node status, cyclin D1, ER and PR (progesterone receptor) expression. Surprisingly, there was no difference in tamoxifen response for patients with high or low HIF-1 alpha expressing tumours. In lymph node-positive patients as well as NHG 1/2 tumours, high HIF-1 alpha protein expression was significantly associated with an impaired recurrence-free survival (p = 0.014, 0.0.18). When analyzing the subgroup of NHG 1/2 tumours, a high HIF-1 alpha expression was the only independent significant prognostic marker in multivariate analysis, including standard prognostic markers, suggesting that HIF-1a might be a useful prognostic marker in this subgroup of breast cancer, with a rather good but diverse prognosis. (c) 2005 Wiley-Liss, Inc.}},
author = {{Kronblad, Åsa and Jirström, Karin and Rydén, Lisa and Nordenskjold, Bo and Landberg, Göran}},
issn = {{0020-7136}},
keywords = {{tamoxifen treatment; prognosis; HIF-1 alpha; breast cancer}},
language = {{eng}},
number = {{10}},
pages = {{2609--2616}},
publisher = {{John Wiley & Sons Inc.}},
series = {{International Journal of Cancer}},
title = {{Hypoxia inducible factor-1alpha is a prognostic marker in premenopausal patients with intermediate to highly differentiated breast cancer but not a predictive marker for tamoxifen response.}},
url = {{https://lup.lub.lu.se/search/files/2701505/625181.pdf}},
doi = {{10.1002/ijc.21676}},
volume = {{118}},
year = {{2006}},
}