title: Role of combination therapy with aromatase and cyclooxygenase-2 inhibitors in patients with metastatic breast cancer.
abstract: 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.
authors.affiliation: Department of Medical Oncology, Centre Hospitalier Lyon Sud, Pierre-Bénite, France. claire.leger-falandry@ens-lyon.fr
authors.forename: C
authors.initials: C
authors.lastname: Falandry
authors.forename: P A
authors.initials: PA
authors.lastname: Canney
authors.forename: G
authors.initials: G
authors.lastname: Freyer
authors.forename: L Y
authors.initials: LY
authors.lastname: Dirix
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D016896:Treatment Outcome
chemical_list: D047072:Aromatase Inhibitors; D016861:Cyclooxygenase Inhibitors