Does the addition of COX-2 inhibitors alter the resistance to aromatase inhibitors?

Abstract

11511 Background: This study aimed to investigate whether the addition of COX-2 inhibitor to aromatase inhibitor alter the resistance to aromatase inhibitor, developed during first or second line hormonal treatment of estrogen (ER) and/or progesterone receptor (PR) positive metastatic breast cancer cases. Methods: ER and/or PR positive breast cancer patients with known high baseline CA 15–3 levels due to the tumor and receiving a first or second line (after first line tamoxifen) aromatase inhibitor due to soft tissue (lymphatic tissue, skin) or bone metastasis were evaluated in this study. A recurrent increase in CA 15–3 levels without tumor progression following an initial decrease in CA 15–3 levels was observed in 7 patients and this was considered as resistance to the aromatase inhibitor. For this reason, a COX- 2 inhibitor was added to either letrozole (5/7) or anastrozole (2/7) treatment. The aromatase inhibitor and COX-2 inhibitor combination (celecoxib 200 mg bid, 5/7 cases; rofecoxib 50 mg od, 2/7 cases) was used for 3 months. CA 15–3 levels and tumor response of these 7 cases was re- evaluated at the end of 3 months. Results: None of the seven cases had a decrease in CA 15–3 levels following the 3 months of aromatase inhibitor plus COX-2 inhibitor combination treatment, instead all cases had their levels increased. In addition, none of the 7 cases had clinical or radiological tumor response, all had tumor progression. Treatment was continued by either third line hormone treatment (4/7) or chemotherapy (3/7). Conclusions: COX-2 inhibitors are suggested to potentiate endocrine treatment since the overexpression of COX-2 contributes to the increased expression of aromatase in the breast tumor tissue. Thus, the combination of an aromatase inhibitor and a COX-2 inhibitor may be useful in the hormonal treatment of breast cancer. However, present study failed to demonstrate alteration of the developed aromatase resistance by the addition of a COX-2 inhibitor. No significant financial relationships to disclose.