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CA IX is an independent prognostic marker in premenopausal breast cancer patients with one to three positive lymph nodes and a putative marker of radiation resistance

Brennan, Donal J. ; Jirström, Karin LU orcid ; Kronblad, Åsa LU ; Millikan, Robert C. ; Landberg, Göran LU ; Duffy, Michael J. ; Rydén, Lisa LU orcid ; Gallagher, William M. and O'Brien, Sallyann L. (2006) In Clinical Cancer Research 12(21). p.6421-6431
Abstract
Purpose: Hypoxia in breast cancer is associated with poor prognosis and down-regulation of the estrogen receptor. Carbonic anhydrase IX (CA IX) is a hypoxia-inducible gene that has been associated with poor outcome in many epithelial cancers. Previous studies of CA IX in breast cancer have been carried out on mixed cohorts of premenopausal and postmenopausal patients with locally advanced disease and varying treatment regimens. We examined the potential prognostic and predictive role of CA IX in premenopausal breast cancer patients. Experimental Design: Using tissue microarrays, we analyzed CA IX expression in 400 stage 11 breast cancers from premenopausal women. The patients had previously participated in a randomized control trial... (More)
Purpose: Hypoxia in breast cancer is associated with poor prognosis and down-regulation of the estrogen receptor. Carbonic anhydrase IX (CA IX) is a hypoxia-inducible gene that has been associated with poor outcome in many epithelial cancers. Previous studies of CA IX in breast cancer have been carried out on mixed cohorts of premenopausal and postmenopausal patients with locally advanced disease and varying treatment regimens. We examined the potential prognostic and predictive role of CA IX in premenopausal breast cancer patients. Experimental Design: Using tissue microarrays, we analyzed CA IX expression in 400 stage 11 breast cancers from premenopausal women. The patients had previously participated in a randomized control trial comparing 2 years of tamoxifen to no systemic adjuvant treatment. Median follow-up was 13.9 years. Results: CA IX expression correlated positively with tumor size, grade, hypoxia-inducible factor 1 alpha Ki-67, cyclin E, and cyclin A2 expression. CA IX expression correlated negatively with cyclin D1, estrogen receptor, and progesterone receptor. CA IX expression was associated with a reduced relapse-free survival (P = 0.032), overall survival (P = 0.022), and breast cancer specific survival (P = 0.005). Multivariate analysis revealed that CA IX was an independent prognostic marker in untreated patients with one to three positive lymph nodes (hazard ratio, 3.2; 95% confidence interval, 1.15-9.13; P = 0.027). Conclusion: CA IX is marker of poor prognosis in premenopausal breast cancer patients and it is an independent predictor of survival in patients with one to three positive lymph nodes. As all these patients received locoregional radiation therapy, CA IX may be associated with resistance to radiotherapy. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Cancer Research
volume
12
issue
21
pages
6421 - 6431
publisher
American Association for Cancer Research
external identifiers
  • wos:000241935100017
  • scopus:33751277287
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-06-0480
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), Pathology, (Lund) (013030000), Surgery (Lund) (013009000), Oncology, MV (013035000)
id
ab3482fc-15d7-4119-9b46-56d7e20067e6 (old id 377185)
alternative location
http://clincancerres.aacrjournals.org/cgi/content/abstract/12/21/6421
date added to LUP
2016-04-01 12:27:53
date last changed
2024-01-08 21:22:03
@article{ab3482fc-15d7-4119-9b46-56d7e20067e6,
  abstract     = {{Purpose: Hypoxia in breast cancer is associated with poor prognosis and down-regulation of the estrogen receptor. Carbonic anhydrase IX (CA IX) is a hypoxia-inducible gene that has been associated with poor outcome in many epithelial cancers. Previous studies of CA IX in breast cancer have been carried out on mixed cohorts of premenopausal and postmenopausal patients with locally advanced disease and varying treatment regimens. We examined the potential prognostic and predictive role of CA IX in premenopausal breast cancer patients. Experimental Design: Using tissue microarrays, we analyzed CA IX expression in 400 stage 11 breast cancers from premenopausal women. The patients had previously participated in a randomized control trial comparing 2 years of tamoxifen to no systemic adjuvant treatment. Median follow-up was 13.9 years. Results: CA IX expression correlated positively with tumor size, grade, hypoxia-inducible factor 1 alpha Ki-67, cyclin E, and cyclin A2 expression. CA IX expression correlated negatively with cyclin D1, estrogen receptor, and progesterone receptor. CA IX expression was associated with a reduced relapse-free survival (P = 0.032), overall survival (P = 0.022), and breast cancer specific survival (P = 0.005). Multivariate analysis revealed that CA IX was an independent prognostic marker in untreated patients with one to three positive lymph nodes (hazard ratio, 3.2; 95% confidence interval, 1.15-9.13; P = 0.027). Conclusion: CA IX is marker of poor prognosis in premenopausal breast cancer patients and it is an independent predictor of survival in patients with one to three positive lymph nodes. As all these patients received locoregional radiation therapy, CA IX may be associated with resistance to radiotherapy.}},
  author       = {{Brennan, Donal J. and Jirström, Karin and Kronblad, Åsa and Millikan, Robert C. and Landberg, Göran and Duffy, Michael J. and Rydén, Lisa and Gallagher, William M. and O'Brien, Sallyann L.}},
  issn         = {{1078-0432}},
  language     = {{eng}},
  number       = {{21}},
  pages        = {{6421--6431}},
  publisher    = {{American Association for Cancer Research}},
  series       = {{Clinical Cancer Research}},
  title        = {{CA IX is an independent prognostic marker in premenopausal breast cancer patients with one to three positive lymph nodes and a putative marker of radiation resistance}},
  url          = {{http://dx.doi.org/10.1158/1078-0432.CCR-06-0480}},
  doi          = {{10.1158/1078-0432.CCR-06-0480}},
  volume       = {{12}},
  year         = {{2006}},
}