Aromatase inhibitors (AIs) are well established in the treatment of metastatic
hormone-sensitive
breast cancer in postmenopausal women.
Cyclooxygenase (COX)-2 inhibitors have demonstrated efficacy in reducing
cancer risk in animal and human studies. In several preclinical studies, combination AI plus
COX-2 inhibitor therapy has shown a synergistic antitumor effect. This review describes the utility of AI plus
COX-2 inhibitor therapy and discusses the completed and ongoing clinical trials investigating treatment with the AI
exemestane and the
COX-2 inhibitor celecoxib in the neo-adjuvant and metastatic
breast cancer settings. In general, combination
therapy had comparable or better efficacy compared with AI monotherapy using the end points of progression-free survival, overall response rate, clinical benefit rate, time to progression, and duration of clinical benefit. All
therapies were well tolerated. There appeared to be a beneficial impact on serum
lipid levels for patients receiving combination
therapy in a neo-adjuvant trial despite the known cardiovascular toxicity risk associated with
COX-2 inhibitors. In conclusion, AIs plus
COX-2 inhibitors have shown promising efficacy and safety for the treatment of patients with metastatic
breast cancer. Careful monitoring during future trials will be necessary to accurately assess the risk-benefit ratio of combination
therapy.