RESUMO
Background: Tumoral hypoxia is associated with aggressiveness in many cancers including breast cancer. However, measuring hypoxia is complicated. Carbonic anhydrase IX (CAIX) is a reliable endogenous marker of hypoxia under the control of the master regulator hypoxia-inducible factor-1α (HIF-1α). The expression of CAIX is associated with poor prognosis in many solid malignancies; however, its role in breast cancer remains controversial. Methods: The present study performed a meta-analysis to evaluate the correlation between CAIX expression and disease-free survival (DFS) and overall survival (OS) in breast cancer. Results: A total of 2,120 publications from EMBASE, PubMed, Cochrane, and Scopus were screened. Of these 2,120 publications, 272 full texts were reviewed, and 27 articles were included in the meta-analysis. High CAIX was significantly associated with poor DFS (HR = 1.70, 95% CI = 1.39-2.07, p < 0.00001) and OS (HR = 2.02, 95% CI 1.40-2.91, p = 0.0002) in patients with breast cancer. When stratified by subtype, the high CAIX group was clearly associated with shorter DFS (HR = 2.09, 95% CI =1.11-3.92, p = 0.02) and OS (HR = 2.50, 95% CI =1.53-4.07, p = 0.0002) in TNBC and shorter DFS in ER+ breast cancer (HR = 1.81 95% CI =1.38-2.36, p < 0.0001). Conclusion: High CAIX expression is a negative prognostic marker of breast cancer regardless of the subtypes.
RESUMO
BACKGROUND AND PURPOSE: Web-based prognostic calculators have been developed to inform about the use of adjuvant systemic treatments in breast cancer. CancerMath and PREDICT are two examples of web-based prognostic tools that predict patient survival up to 15 years after an initial diagnosis of breast cancer. The aim of this study is to validate the use of CancerMath and PREDICT as prognostic tools in Thai breast cancer patients. PATIENTS AND METHODS: A total of 615 patients who underwent surgical treatment for stage I to III breast cancer from 2003 to 2011 at the Division of Head Neck and Breast Surgery, Department of Surgery, Siriraj Hospital, Mahidol University, Thailand were recruited. A model-predicted overall survival rate (OS) and the actual OS of the patients were compared. The efficacy of the model was evaluated using receiver-operating characteristic (ROC) analysis. RESULTS: For CancerMath, the predicted 5-year OS was 88.9% and the predicted 10-year OS was 78.3% (p<0.001). For PREDICT, the predicted 5-year OS was 83.1% and the predicted 10-year OS was 72.0% (p<0.001). The actual observed 5-year OS was 90.8% and the observed 10-year OS was 82.6% (p<0.001). CancerMath demonstrated better predictive performance than PREDICT in all subgroups for both 5- and 10-year OS. In addition, there was a marked difference between CancerMath and observed survival rates in patients who were older as well as patients who were stage N3. The area under the ROC curve for 5-year OS in CancerMath and 10-year OS was 0.74 (95% CI; 0.65-0.82) and 0.75 (95% CI; 0.68-0.82). In the PREDICT group, the area under the ROC curve for 5-year OS was 0.78 (95% CI; 0.71-0.85) and for 10-year OS, it was 0.78 (95% CI; 0.71-0.84). CONCLUSION: CancerMath and PREDICT models both underestimated the OS in Thai breast cancer patients. Thus, a novel prognostic model for Thai breast cancer patients is required.