COX2 expression in prognosis and in prediction to endocrine therapy in early breast cancer patients

Nes, Johanna G. H. van; Kruijf, Esther M. de; Faratian, Dana; Velde, Cornelis J.H. van de; Putter, Hein; Falconer, C. W. A.; Smit, Vincent T.H.B.M.; Kay, Charlene; Vijver, Marc J. van de; Kuppen, Peter J. K.; Bartlett, John M.S.

doi:10.1007/s10549-010-0854-7

Cited by 48 publications

(53 citation statements)

References 30 publications

(33 reference statements)

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“…A total of 33.0% of our sample cohort exhibited COX-2 expression (using the 5% threshold), which is similar to the results of previous studies (24)(25)(26)(27)(28)(29)(31)(32)(33)(34). In congruence with previously published reports, we observed a significant association between COX-2 expression and high tumor grade (26)(27)(28)30,32,33) and also identified a significant association between COX-2 expression and TNBC. The association between TNBC status and high tumor grade (OR=8.89, 95% CI: 3.12-28.55; P<0.001) was in agreement with results of larger studies (12,13,15,16,18,22).…”

Section: Discussionsupporting

confidence: 91%

“…Studies using in vitro breast cancer cell lines and in vivo mouse models have demonstrated that COX-2 overexpression plays key roles in tumorigenesis by stimulating epithelial cell proliferation, inhibiting apoptosis, stimulating angiogenesis, increasing multidrug resistance and enhancing cell motility and invasion (15)(16)(17)(18)(19)(20)(21)(22)(23). The evidence supporting the role of COX-2 in breast cancer progression has also been demonstrated in clinical studies; patients with COX-2-expressing primary tumors exhibited shortened disease-free and overall survival (24)(25)(26)(27)(28)(29)(30).…”

Section: Introductionmentioning

confidence: 90%

“…Triple-negative status and COX-2 expression have both been significantly associated with an unfavorable outcome for non-metastatic breast cancer patients (30,35). The purpose of our study was to determine whether COX-2 protein expression in primary breast cancer is associated with TNBC.…”

Section: Introductionmentioning

confidence: 99%

“…COX-2 expression is frequently associated with high histological grade and large tumor size (24)(25)(26)(27)(28)30,32,33) and, to a lesser degree, negative ER status (24,26,27,30,31,33). The association between COX-2 expression and HER2/neu expression is not conclusive; in two large studies, COX-2 was significantly associated with increased HER2/neu expression (27,33), while no significant association was observed in a number of other studies (24,25,28,(30)(31)(32). These disparate results emphasize the need for standardized, reproducible assays for COX-2 assessment, which may enable meaningful associations and interpretations.…”

Section: Introductionmentioning

confidence: 99%

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Cyclooxygenase-2 expression in non-metastatic triple-negative breast cancer patients

Mosalpuria

Hall

Krishnamurthy

et al. 2014

Molecular and Clinical Oncology

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Abstract. Triple-negative breast cancer (TNBC) is characterised by lack of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER)2/neu gene amplification. TNBC patients typically present at a younger age, with a larger average tumor size, higher grade and higher rates of lymph node positivity compared to patients with ER/PR-positive tumors. Cyclooxygenase (COX)-2 regulates the production of prostaglandins and is overexpressed in a variety of solid tumors. In breast cancer, the overexpression of COX-2 is associated with indicators of poor prognosis, such as lymph node metastasis, poor differentiation and large tumor size. Since both TNBC status and COX-2 overexpression are known poor prognostic markers in primary breast cancer, we hypothesized that the COX-2 protein is overexpressed in the primary tumors of TNBC patients. The purpose of this study was to determine whether there exists an association between TNBC status and COX-2 protein overexpression in primary breast cancer. We prospectively evaluated COX-2 expression levels in primary tumor samples obtained from 125 patients with stage I-III breast cancer treated between February, 2005 and October, 2007. Information on clinicopathological factors was obtained from a prospective database. Baseline tumor characteristics and patient demographics were compared between TNBC and non-TNBC patients using the Chi-square and Fisher's exact tests. In total, 60.8% of the patients were classified as having ER-positive tumors, 51.2% were PR-positive, 14.4% had HER-2/neu amplification and 28.0% were classified as TNBC. COX-2 overexpression was found in 33.0% of the patients. TNBC was associated with COX-2 overexpression (P=0.009), PR expression (P= 0.048) and high tumor grade (P= 0.001). After adjusting for age, menopausal status, body mass index (BMI), lymph node status and neoadjuvant chemotherapy (NACT), TNBC was an independent predictor of COX-2 overexpression (P= 0.01). In conclusion, the association between TNBC and COX-2 overexpression in operable breast cancer supports further investigation into COX-2-targeted therapy for patients with TNBC.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cyclooxygenase-2 expression in non-metastatic triple-negative breast cancer patients

Mosalpuria

Hall

Krishnamurthy

et al. 2014

Molecular and Clinical Oncology

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“…Patients with bilateral tumors or a prior history of cancer (other than basal cell carcinoma or cervical carcinoma in situ) were excluded. The following data were known: age, tumor grade, histological type, Tumor-Node-Metastasis stage, local and systemic therapy, locoregional/distant tumor recurrence, secondary tumor, survival, and expression of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) (23). All tumors were graded according to current pathological standards by a pathologist (V.T.H.B.M.…”

Section: Patients and Tumorsmentioning

confidence: 99%

HLA-E and HLA-G Expression in Classical HLA Class I-Negative Tumors Is of Prognostic Value for Clinical Outcome of Early Breast Cancer Patients

Kruijf¹,

Sajet²,

Nes³

et al. 2010

The Journal of Immunology

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235

195

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Nonclassical HLAs, HLA-E and HLA-G, are known to affect clinical outcome in various tumor types. We examined the clinical impact of HLA-E and HLA-G expression in early breast cancer patients, and related the results to tumor expression of classical HLA class I. Our study population (n = 677) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1995. Tissue microarray sections of arrayed tumor and normal control material were immunohistochemically stained for HLA-E and HLA-G. For evaluation of HLA-E and HLA-G and the combined variable, HLA-EG, a binary score was used. Expression of classical HLA class I molecules was determined previously. HLA-E, HLA-G, and HLA-EG on breast tumors were classified as expression in 50, 60, and 23% of patients, respectively. Remarkably, only in patients with loss of classical HLA class I tumor expression, expression of HLA-E (p = 0.027), HLA-G (p = 0.035), or HLA-EG (p = 0.001) resulted in a worse relapse-free period. An interaction was found between classical and nonclassical HLA class I expression (p = 0.002), suggestive for a biological connection. We have demonstrated that, next to expression of classical HLA class I, expression of HLA-E and HLA-G is an important factor in the prediction of outcome of breast cancer patients. These results provide further evidence that breast cancer is immunogenic, but also capable of evading tumor eradication by the host’s immune system, by up- or downregulation of HLA class Ia and class Ib loci.

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Effect of Celecoxib vs Placebo as Adjuvant Therapy on Disease-Free Survival Among Patients With Breast Cancer

et al. 2021

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for the Randomized European Celecoxib Trial (REACT) Trial Management Group and Investigators IMPORTANCE Patients with breast cancer remain at risk of relapse after adjuvant therapy. Celecoxib has shown antitumor effects in preclinical models of human breast cancer, but clinical evidence is lacking.OBJECTIVE To evaluate the role of celecoxib as an addition to conventional therapy for women with ERBB2 (formerly HER2)-negative primary breast cancer. DESIGN, SETTING, AND PARTICIPANTSThe Randomized European Celecoxib Trial (REACT) was a phase 3, randomized, double-blind study conducted in 160 centers across the UK and Germany testing 2 years of adjuvant celecoxib vs placebo among 2639 patients recruited between January 19, 2007, and November 1, 2012, with follow-up 10 years after treatment completion. Eligible patients had completely resected breast cancer with local and systemic therapy according to local practice. Patients with ERBB2-positive or node-negative and T1, grade 1 tumors were not eligible. Randomization was in a 2:1 ratio between celecoxib or placebo. Statistical analysis was performed from May 5, 2019, to March 5, 2020.INTERVENTIONS Patients received celecoxib, 400 mg, or placebo once daily for 2 years. MAIN OUTCOMES AND MEASURESThe primary end point was disease-free survival (DFS), analyzed in the intention-to-treat population using Cox proportional hazards regression and log-rank analysis. Follow-up is complete.RESULTS A total of 2639 patients (median age, 55.2 years [range, 26.8-86.0 years]) were recruited; 1763 received celecoxib, and 876 received placebo. Most patients' tumors (1930 [73%]) were estrogen receptor positive or progesterone receptor positive and ERBB2 negative. A total of 1265 patients (48%) had node-positive disease, and 1111 (42%) had grade 3 tumors. At a median follow-up of 74.3 months (interquartile range, 61.4-93.6 years), DFS events had been reported for 487 patients (19%): 18% for those who received celecoxib (n = 323; 5-year DFS rate = 84%) vs 19% for those who received placebo (n = 164; 5-year DFS rate = 83%); the unadjusted hazard ratio was 0.97 (95% CI, 0.80-1.17; log-rank P = .75). Rates of toxic effects were low across both treatment groups, with no evidence of a difference. CONCLUSIONS AND RELEVANCEIn this randomized clinical trial, patients showed no evidence of a DFS benefit for 2 years' treatment with celecoxib compared with placebo as adjuvant treatment of ERBB2-negative breast cancer. Longer-term treatment or use of a higher dose of celecoxib may lead to a DFS benefit, but further studies would be required to test this possibility.

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COX2 expression in prognosis and in prediction to endocrine therapy in early breast cancer patients

Cited by 48 publications

References 30 publications

Cyclooxygenase-2 expression in non-metastatic triple-negative breast cancer patients

Cyclooxygenase-2 expression in non-metastatic triple-negative breast cancer patients

HLA-E and HLA-G Expression in Classical HLA Class I-Negative Tumors Is of Prognostic Value for Clinical Outcome of Early Breast Cancer Patients

Effect of Celecoxib vs Placebo as Adjuvant Therapy on Disease-Free Survival Among Patients With Breast Cancer

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