Can Celecoxib Be Used to Treat HER2-Negative Breast Cancer?
Posted: Monday, March 18, 2019
Although prostaglandin-endoperoxide synthase 2 (PTGS2) is overexpressed in breast cancer, utilization of the PTGS2 inhibitor celecoxib during chemotherapy seemed to adversely affect survival in patients with breast cancer, particularly those with PTGS2-low and estrogen receptor–negative tumors. Anne-Sophie Hamy, MD, of the Institut Curie, France, and her team published the results of the REMAGUS02 trial in the Journal of Clinical Oncology.
“PTGS2 inhibitors should preferably be avoided during docetaxel use in patients with breast cancer who are undergoing neoadjuvant chemotherapy,” concluded the authors.
A total of 156 patients with HER2-negative breast cancer were treated with sequential neoadjuvant chemotherapy (epirubicin plus cyclophosphamide followed by docetaxel) with or without celecoxib. Breast cancer cell lines were used to validate results in vitro. Results were compared with those from the CALGB 30801 trial utilizing chemotherapy with or without celecoxib in patients with lung cancer.
After 94.5 months of follow-up, the event-free survival was significantly lower for the group treated with celecoxib (hazard ratio = 1.7). There was significant interaction between the COX2 expression and celecoxib use. For patients with low amounts of PTGS2, the event-free survival was lower if they were treated with celecoxib compared with standard treatment (hazard ratio = 3.01). Celecoxib use was a predictor of lower event-free survival, distant relapse–free survival, and overall survival.
Cell lines with low PTGS2 expression had enhanced viability when treated with celecoxib and docetaxel, but this was not true for cell lines with high PTGS2 expression. In addition, the CALGB 30801 trial showed a trend toward worse progression-free survival in patients with low urinary metabolite levels of prostaglandin E2 (PTGS2 product) treated with celecoxib.
Disclosure: The study authors’ disclosure information may be found at ascopubs.org.