Celecoxib With Neoadjuvant Chemotherapy for Breast Cancer Might Worsen Outcomes Differentially by COX-2 Expression and ER Status: Exploratory Analysis of the REMAGUS02 Trial.

TitleCelecoxib With Neoadjuvant Chemotherapy for Breast Cancer Might Worsen Outcomes Differentially by COX-2 Expression and ER Status: Exploratory Analysis of the REMAGUS02 Trial.
Publication TypeJournal Article
Year of Publication2019
AuthorsHamy, Anne-Sophie, Sandrine Tury, Xiaofei Wang, Junheng Gao, Jean-Yves Pierga, Sylvie Giacchetti, Etienne Brain, Barbara Pistilli, Michel Marty, Marc EspiƩ, Gabriel Benchimol, Enora Laas, Marick LaƩ, Bernard Asselain, Brice Aouchiche, Martin Edelman, and Fabien Reyal
JournalJ Clin Oncol
Date Published2019 Mar 10
KeywordsAdult, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Breast Neoplasms, Celecoxib, Cell Line, Tumor, Cell Survival, Chemotherapy, Adjuvant, Clinical Trials, Phase II as Topic, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Disease Progression, Female, Humans, Middle Aged, Neoadjuvant Therapy, Neoplasm Metastasis, Progression-Free Survival, Randomized Controlled Trials as Topic, Receptors, Estrogen, Risk Factors, Time Factors

PURPOSE: The overexpression of cyclooxygenase 2 (COX-2) gene, also known as prostaglandin-endoperoxide synthase 2 ( PTGS2), occurs in breast cancer, but whether it affects response to anticox drugs remains unclear. We investigated the relationships between PTGS2 expression, celecoxib use during neoadjuvant chemotherapy (NAC), and both event-free survival (EFS) and overall survival (OS).MATERIALS AND METHODS: We analyzed a cohort of 156 patients with human epidermal growth factor receptor 2 -negative breast cancer from the REMAGUS02 (ISRCTN Registry No. 10059974) trial with pretreatment PTGS2 expression data. Patients were treated by sequential NAC (epirubicin plus cyclophosphamide followed by docetaxel with or without celecoxib). Experimental validation was performed on breast cancer cell lines. The Cancer and Leukemia Group B (CALGB) 30801 ( ClinicalTrials.gov identifier: NCT01041781) trial that tested chemotherapy with or without celecoxib in patients with lung cancer served as an independent validation cohort.RESULTS: After 94.5 months of follow-up, EFS was significantly lower in the celecoxib group (hazard ratio [HR], 1.7; 95% CI, 1 to 2.88; P = .046). A significant interaction between PTGS2 expression and celecoxib use was detected ( P = .01). In the PTGS2-low group (n = 100), EFS was lower in the celecoxib arm (HR, 3.01; 95% CI, 1.45 to 6.24; P = .002) than in the standard treatment arm. Celecoxib use was an independent predictor of poor EFS, distant relapse-free survival, and OS. Celecoxib in addition to docetaxel enhanced cell viability in PTGS2-low cell lines but not in PTGS2-high cell lines. In CALGB 30801, a trend toward poorer progression-free survival was observed in the patients with low urinary metabolite of prostaglandin E2 who received celecoxib (HR = 1.57; 95% CI, 0.87 to 2.84; P = .13).CONCLUSION: Celecoxib use during chemotherapy adversely affected survival in patients with breast cancer, and the effect was more marked in PTGS2-low and/or estrogen receptor-negative tumors. COX-2 inhibitors should preferably be avoided during docetaxel use in patients with breast cancer who are undergoing NAC.

Alternate JournalJ Clin Oncol
Original PublicationCelecoxib with neoadjuvant chemotherapy for breast cancer might worsen outcomes differentially by COX-2 expression and ER status: Exploratory analysis of the REMAGUS02 trial.
PubMed ID30702971
PubMed Central IDPMC6804843
Grant ListP30 CA006927 / CA / NCI NIH HHS / United States