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The prognostic impact of COX-2 expression in breast cancer depends on oral contraceptive history, preoperative NSAID use, and tumor size

Simonsson, Maria LU ; Björner, Sofie LU ; Markkula, Andrea LU ; Nodin, Björn LU ; Jirström, Karin LU orcid ; Rose, Carsten LU ; Borgquist, Signe LU ; Ingvar, Christian LU and Jernström, Helena LU (2017) In International Journal of Cancer 140(1). p.163-175
Abstract

The association between tumor cyclooxygenase 2 (COX-2) expression and breast cancer prognosis has been inconsistent. The purpose of this study was to evaluate the prognostic significance of COX-2 tumor expression according to adjuvant treatment, and potential effect modifications of non-steroid anti-inflammatory drug (NSAID) use, and other tumor and lifestyle factors. A prospective cohort of 1,116 patients with primary breast cancer in Lund, Sweden, included 2002-2012 was followed until June 2014 (median 5 years). Tumor-specific COX-2 expression was evaluated on tissue microarrays using immunohistochemistry. Associations between COX-2 intensity (negative, weak-moderate, high) and patient and tumor characteristics as well as prognosis... (More)

The association between tumor cyclooxygenase 2 (COX-2) expression and breast cancer prognosis has been inconsistent. The purpose of this study was to evaluate the prognostic significance of COX-2 tumor expression according to adjuvant treatment, and potential effect modifications of non-steroid anti-inflammatory drug (NSAID) use, and other tumor and lifestyle factors. A prospective cohort of 1,116 patients with primary breast cancer in Lund, Sweden, included 2002-2012 was followed until June 2014 (median 5 years). Tumor-specific COX-2 expression was evaluated on tissue microarrays using immunohistochemistry. Associations between COX-2 intensity (negative, weak-moderate, high) and patient and tumor characteristics as well as prognosis were analyzed. Tumor-specific COX-2 expression was available for 911 patients and was significantly associated with higher age at diagnosis and less aggressive tumor characteristics. Higher COX-2 expression was associated with lower risk for breast cancer events during the first five years of follow-up, adjHR 0.60 (95%CI: 0.37-0.97), per category. The association between COX-2 expression and prognosis was significantly modified by oral contraceptive (OC) use (Pinteraction=0.048), preoperative NSAID use (Pinteraction=0.009), and tumor size (Pinteraction=0.039). COX-2 negativity was associated with increased risk for events during the first five years in ever OC users, adjHR 1.94 (1.01-3.72) and during the 11-year follow-up in preoperative NSAID users, adjHR 4.51 (1.18-11.44) as well as in patients with large tumors, adjHR 2.57 (1.28-5.15). In conclusion, this study, one of the largest evaluating COX-2 expression in breast cancer, indicates that the prognostic impact of COX-2 expression depends on host factors and tumor characteristics.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Breast cancer, Cyclooxygenase-2, Non-steroidal anti-inflammatory drugs, Oral contraceptives, Prognosis
in
International Journal of Cancer
volume
140
issue
1
pages
163 - 175
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:27632554
  • wos:000387620600018
  • scopus:84992471330
ISSN
0020-7136
DOI
10.1002/ijc.30432
language
English
LU publication?
yes
id
ce3564dc-8720-41a9-81fd-61ef2588aeea
date added to LUP
2016-11-10 14:14:13
date last changed
2025-01-12 14:55:22
@article{ce3564dc-8720-41a9-81fd-61ef2588aeea,
  abstract     = {{<p>The association between tumor cyclooxygenase 2 (COX-2) expression and breast cancer prognosis has been inconsistent. The purpose of this study was to evaluate the prognostic significance of COX-2 tumor expression according to adjuvant treatment, and potential effect modifications of non-steroid anti-inflammatory drug (NSAID) use, and other tumor and lifestyle factors. A prospective cohort of 1,116 patients with primary breast cancer in Lund, Sweden, included 2002-2012 was followed until June 2014 (median 5 years). Tumor-specific COX-2 expression was evaluated on tissue microarrays using immunohistochemistry. Associations between COX-2 intensity (negative, weak-moderate, high) and patient and tumor characteristics as well as prognosis were analyzed. Tumor-specific COX-2 expression was available for 911 patients and was significantly associated with higher age at diagnosis and less aggressive tumor characteristics. Higher COX-2 expression was associated with lower risk for breast cancer events during the first five years of follow-up, <sub>adj</sub>HR 0.60 (95%CI: 0.37-0.97), per category. The association between COX-2 expression and prognosis was significantly modified by oral contraceptive (OC) use (P<sub>interaction</sub>=0.048), preoperative NSAID use (P<sub>interaction</sub>=0.009), and tumor size (P<sub>interaction</sub>=0.039). COX-2 negativity was associated with increased risk for events during the first five years in ever OC users, <sub>adj</sub>HR 1.94 (1.01-3.72) and during the 11-year follow-up in preoperative NSAID users, <sub>adj</sub>HR 4.51 (1.18-11.44) as well as in patients with large tumors, <sub>adj</sub>HR 2.57 (1.28-5.15). In conclusion, this study, one of the largest evaluating COX-2 expression in breast cancer, indicates that the prognostic impact of COX-2 expression depends on host factors and tumor characteristics.</p>}},
  author       = {{Simonsson, Maria and Björner, Sofie and Markkula, Andrea and Nodin, Björn and Jirström, Karin and Rose, Carsten and Borgquist, Signe and Ingvar, Christian and Jernström, Helena}},
  issn         = {{0020-7136}},
  keywords     = {{Breast cancer; Cyclooxygenase-2; Non-steroidal anti-inflammatory drugs; Oral contraceptives; Prognosis}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{163--175}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{International Journal of Cancer}},
  title        = {{The prognostic impact of COX-2 expression in breast cancer depends on oral contraceptive history, preoperative NSAID use, and tumor size}},
  url          = {{https://lup.lub.lu.se/search/files/24478186/16769225.pdf}},
  doi          = {{10.1002/ijc.30432}},
  volume       = {{140}},
  year         = {{2017}},
}