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The purpose of this study is to investigate the role of carbonic anhydrase IX (CAIX) expression in predicting the response to epirubicin and disease-free survival (DFS) in breast cancer patients enrolled in a single institution trial of primary anthracycline and tamoxifen therapy. CAIX expression was assessed in 183 patients with T2-4 N0-1 breast cancer enrolled in a randomized trial comparing four cycles of single agent epirubicin versus epirubicin+tamoxifen as primary systemic treatment. All patients received postoperatively four cycles of the four weekly i.v. cyclophosphamide, methotrexate, 5-fluorouracil regimen. Patients with estrogen receptor (ER)-positive primary tumors received 5 years of adjuvant tamoxifen. Pretreatment, p53 (P=0.007), c-erbB2 (P<0.01), and Ki67 (P=0.02) were directly associated with CAIX expression, while bcl2 (P<0.000) and ER (P=0.000) and progesterone receptor (PgR; P<0.01) were inversely correlated. In multivariate analysis, only high p53 and low bcl2 were independently associated with CAIX positivity. CAIX immunostaining was significantly associated with poor outcome for DFS (P<0.002) and overall survival (P=0.001). In multivariate analysis, a significant interaction was found between CAIX and markers of hormone sensitivity, bcl2 (P=0.01), ER (P=0.02), PgR (P=0.02), and lymph node involvement (P=0.04), in predicting DFS. Presently, there are few clinical markers of resistance to tamoxifen treatment in ER-positive tumors. CAIX expression in breast cancer patients shows a negative predictive role of treatment efficacy in ER-positive patients on the adjuvant tamoxifen after primary chemo-endocrine therapy. Studies investigating the effects of pH on tamoxifen uptake and the effects of therapy with CA inhibitors are planned.

Original publication

DOI

10.1677/erc.1.01216

Type

Journal article

Journal

Endocr Relat Cancer

Publication Date

09/2006

Volume

13

Pages

921 - 930

Keywords

Antibiotics, Antineoplastic, Antigens, Neoplasm, Antineoplastic Agents, Hormonal, Antineoplastic Combined Chemotherapy Protocols, Biopsy, Breast Neoplasms, Carbonic Anhydrase IX, Carbonic Anhydrases, Disease-Free Survival, Epirubicin, Female, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Neoplasm Metastasis, Neoplasm Staging, Postmenopause, Premenopause, Receptors, Estrogen, Survival Analysis, Tamoxifen, Treatment Outcome