Circulating Carbonic Anhydrase IX and Antiangiogenic Therapy in Breast Cancer

• Published in: Disease markers Vol. 2016; no. 2016; pp. 1 - 7
• Main Authors: Stopeck, Alison T., Iannone, Maria, Livingston, Robert, Chalasani, Pavani, Marron, Marilyn, Brown-Glaberman, Ursa, Specht, Jennifer
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2016; John Wiley & Sons, Inc
• Subjects: Adult; Aged; Angiogenesis Inhibitors - therapeutic use; Anthracyclines; Antigens, Neoplasm - blood; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - enzymology; Cancer; Carbonic Anhydrase IX; Carbonic Anhydrases - blood; Chemotherapy; Cyclophosphamide - therapeutic use; Doxorubicin - therapeutic use; Enzyme-linked immunosorbent assay; Female; Health aspects; Humans; Indoles - therapeutic use; Metastasis; Middle Aged; Neoadjuvant Therapy; Neoplasm Metastasis; Paclitaxel - therapeutic use; Prognosis; Pyrroles - therapeutic use; Sunitinib
• ISSN: 0278-0240; 1875-8630; 1875-8630
• DOI: 10.1155/2016/9810383

Introduction. Carbonic anhydrase IX (CAIX) is a hypoxia regulated metalloenzyme integral to maintaining cellular pH. Increased CAIX expression is associated with poor prognosis in breast cancer. To explore CAIX as a biomarker for breast cancer therapies, we measured plasma CAIX levels in healthy control subjects and in breast cancer patients. Methods. In control subjects we evaluated plasma CAIX stability via commercially available ELISA. We then similarly quantified plasma CAIX levels in (1) locally advanced breast cancer (LABC) patients treated with neoadjuvant paclitaxel + sunitinib (T + S) followed by doxorubicin and cyclophosphamide (AC); (2) metastatic breast cancer (MBC) patients treated with systemic chemotherapy. Results. Plasma CAIX levels were stable at room temperature for at least 48 hours in control subjects. Mean baseline plasma CAIX levels were lower in controls compared to patients with LABC or MBC. In LABC, CAIX levels rose significantly in response to administration of antiangiogenic therapy (T + S) ( p = 0.02 ) but not AC ( p = 0.37 ). In patients with MBC treated without an antiangiogenic agent CAIX levels did not change with therapy. Conclusions. Our results suggest that CAIX may be an easily obtained, stable measure of tumor associated hypoxia as well as a useful pharmacodynamic biomarker for antiangiogenic therapy.