BACKGROUND: We aimed to identify, through a review of the literature, candidate genes for a prospective predictive chemosensitivity test in patients with breast cancer. METHODS: Papers demonstrating an association between gene alterations in tumor tissue and clinical chemosensitivity in breast cancer patients were selected by Medline searches. We calculated odds ratios (ORs) and their 95% confidence intervals (CIs) of response rates for patients who had tumors with or without gene alteration. Combined ORs and CIs were estimated using the DerSimonian-Laird method. RESULTS: A total of 18 genes were evaluated for association with clinical chemosensitivity in 6378 patients registered in 69 studies. The median (range) number of patients in each study was 73 (29-319). Overexpression of ABCB1 (P-glycoprotein) was associated with poor responses to first-line chemotherapy (combined OR [CI], 0.16 [0.05-0.59]; n = 322). Overexpression and amplification of TOP2A (topoisomerase II-alfa) were more frequently observed in patients who responded to first-line chemotherapy (combined OR [CI], 2.73 [1.02-7.27]; n = 323). Overexpression of ERBB2 (c-erbB2) was associated with favorable responses in patients treated with both first-line anthracycline-based chemotherapy and second-line taxane-based chemotherapy (combined ORs [CIs], 1.60 [1.19-2.17]; n = 1807 and 2.24 [1.06-4.74]; n = 259, respectively). BCL2 overexpression was associated with resistance to first-line chemotherapy (combined OR [CI], 0.44 [0.21-0.91]; n = 816). CONCLUSION: ABCB1, TOP2A, ERBB2, and BCL2 were good candidates for future clinical trials of predictive chemosensitivity tests in patients with breast cancer.
BACKGROUND: We aimed to identify, through a review of the literature, candidate genes for a prospective predictive chemosensitivity test in patients with breast cancer. METHODS: Papers demonstrating an association between gene alterations in tumor tissue and clinical chemosensitivity in breast cancerpatients were selected by Medline searches. We calculated odds ratios (ORs) and their 95% confidence intervals (CIs) of response rates for patients who had tumors with or without gene alteration. Combined ORs and CIs were estimated using the DerSimonian-Laird method. RESULTS: A total of 18 genes were evaluated for association with clinical chemosensitivity in 6378 patients registered in 69 studies. The median (range) number of patients in each study was 73 (29-319). Overexpression of ABCB1 (P-glycoprotein) was associated with poor responses to first-line chemotherapy (combined OR [CI], 0.16 [0.05-0.59]; n = 322). Overexpression and amplification of TOP2A (topoisomerase II-alfa) were more frequently observed in patients who responded to first-line chemotherapy (combined OR [CI], 2.73 [1.02-7.27]; n = 323). Overexpression of ERBB2 (c-erbB2) was associated with favorable responses in patients treated with both first-line anthracycline-based chemotherapy and second-line taxane-based chemotherapy (combined ORs [CIs], 1.60 [1.19-2.17]; n = 1807 and 2.24 [1.06-4.74]; n = 259, respectively). BCL2 overexpression was associated with resistance to first-line chemotherapy (combined OR [CI], 0.44 [0.21-0.91]; n = 816). CONCLUSION:ABCB1, TOP2A, ERBB2, and BCL2 were good candidates for future clinical trials of predictive chemosensitivity tests in patients with breast cancer.
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