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Celecoxib in breast cancer prevention and therapy.

ABSTRACT: Breast cancer has a high incidence worldwide. The results of substantial studis reveal that inflammation plays an important role in the initiation, development, and aggressiveness of many malignancies. The use of celecoxib, a novel NSAID, is repetitively associated with the reduced risk of the occurrence and progression of a number of types of cancer, particularly breast cancer. This observation is also substantiated by various meta-analyses. Clinical trials have been implemented on integration treatment of celecoxib and shown encouraging results. Celecoxib could be treated as a potential candidate for antitumor agent. There are, nonetheless, some unaddressed questions concerning the precise mechanism underlying the anticancer effect of celecoxib as well as its activity against different types of cancer. In this review, we discuss different mechanisms of anticancer effect of celecoxib as well as preclinical/clinical results signifying this beneficial effect.

SUBMITTER: Li J

PROVIDER: S-EPMC6208493 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Celecoxib in breast cancer prevention and therapy.

Li Jieqing J Hao Qiongyu Q Cao Wei W Vadgama Jaydutt V JV Wu Yong Y

Cancer management and research 20181026

Breast cancer has a high incidence worldwide. The results of substantial studis reveal that inflammation plays an important role in the initiation, development, and aggressiveness of many malignancies. The use of celecoxib, a novel NSAID, is repetitively associated with the reduced risk of the occurrence and progression of a number of types of cancer, particularly breast cancer. This observation is also substantiated by various meta-analyses. Clinical trials have been implemented on integration ...[more]

PMID: 30464589

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Project description:ImportancePatients 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.ObjectiveTo 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.InterventionsPatients 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.ResultsA 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.Trial registrationClinicalTrials.gov Identifier: NCT02429427 and isrctn.org Identifier: ISRCTN48254013.

Project description:Anthracyclines are associated with cardiotoxic effects. Cardiovascular biomarkers may reflect myocardial injury, dysfunction, inflammation, and fibrosis and may precede and predict the development of left ventricular impairment. The aim of this study was to assess: (1) longitudinal change in circulating cardiovascular biomarkers, (2) the effect of metoprolol succinate and candesartan cilexetil on the biomarker response, and (3) the associations between on-treatment changes in biomarker concentrations and subsequent left ventricular dysfunction in patients with early breast cancer receiving anthracyclines.This report encompasses 121 women included in the 2×2 factorial, placebo-controlled, double-blind PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial with metoprolol and candesartan given concomitantly with anticancer therapy containing the anthracycline, epirubicin (total cumulative dose, 240-400 mg/m2). Cardiovascular magnetic resonance, echocardiography images, and circulating levels of biomarkers were obtained before and after anthracycline treatment. Cardiac troponins I and T, B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide, C-reactive protein, and galectin-3 increased during anthracycline therapy (all P<0.05). The troponin response was attenuated by metoprolol (P<0.05), but not candesartan. There was no association between change in biomarker concentrations and change in cardiac function during anthracycline therapy.Treatment with contemporary anthracycline doses for early breast cancer is associated with increase in circulating cardiovascular biomarkers. This increase is, however, not associated with early decline in ventricular function. Beta-blockade may attenuate early myocardial injury, but whether this attenuation translates into reduced risk of developing ventricular dysfunction in the long term remains unclear.URL: http://www.clinicaltrial.gov. Unique identifier: NCT01434134.

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Celecoxib in breast cancer prevention and therapy.

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Celecoxib in breast cancer prevention and therapy.

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