TY - JOUR
T1 - Role of carbonic anhydrase IX expression in prediction of the efficacy and outcome of primary epirubicin/tamoxifen therapy for breast cancer
AU - Generali, Daniele
AU - Fox, Stephen B.
AU - Berruti, Alfredo
AU - Brizzi, Maria P.
AU - Campo, Leticia
AU - Bonardi, Simone
AU - Wigfield, Simon M.
AU - Bruzzi, Paolo
AU - Bersiga, Alessandra
AU - Allevi, Giovanni
AU - Milani, Manuela
AU - Aguggini, Sergio
AU - Dogliotti, Luigi
AU - Bottini, Alberto
AU - Harris, Adrian L.
PY - 2006/9
Y1 - 2006/9
N2 - 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.
AB - 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.
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U2 - 10.1677/erc.1.01216
DO - 10.1677/erc.1.01216
M3 - Article
C2 - 16954440
AN - SCOPUS:33751111993
VL - 13
SP - 921
EP - 930
JO - Endocrine-Related Cancer
JF - Endocrine-Related Cancer
SN - 1351-0088
IS - 3
ER -