title: Circulating Carbonic Anhydrase IX and Antiangiogenic Therapy in Breast Cancer.
abstract: BACKGROUND
  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.
authors.affiliation: University of New Mexico Cancer Center, Albuquerque, NM 87131, USA.
authors.forename: Ursa
authors.initials: U
authors.lastname: Brown-Glaberman
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ 85719, USA.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Marron
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ 85719, USA.
authors.forename: Pavani
authors.initials: P
authors.lastname: Chalasani
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ 85719, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Livingston
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ 85719, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Iannone
authors.affiliation: Fred Hutchinson University of Washington Cancer Consortium, Seattle, WA 98019, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Specht
authors.affiliation: Stony Brook Cancer Center, SUNY Stony Brook, Stony Brook, NY 11794, USA.
authors.forename: Alison T
authors.initials: AT
authors.lastname: Stopeck
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000097:blood*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D000077210:Sunitinib
chemical_list: D020533:Angiogenesis Inhibitors; D000951:Antigens, Neoplasm; D007211:Indoles; D011758:Pyrroles; D004317:Doxorubicin; D003520:Cyclophosphamide; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D017239:Paclitaxel; D000077210:Sunitinib