Preventive effect of low-dose carvedilol combined with candesartan on the cardiotoxicity of anthracycline drugs in the adjuvant chemotherapy of breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effect of low-dose carvedilol combined with candesartan in the prevention of acute and chronic cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer.</p><p><b>METHODS</b>Forty patients were randomly divided into two groups: the experimental group with chemotherapy plus low-dose carvedilol combined with candesartan (20 cases) and control group with chemotherapy alone (20 cases). The same chemotherapy was given to the two groups. All the 40 patients had no contraindication for carvedilol and candesartan. Patients of the experimental group received low-dose carvedilol from 2.5 mg orally twice a day at first cycle to 5 mg twice a day gradually if no side reactions, and candesartan 2.5 mg orally once a day. Electrocardiogram, ultrasonic cardiogram, arrhythmia, troponin and non-hematologic toxicity were recorded and compared after the second, forth and sixth cycle of chemotherapy. Each cycle included 21 days.</p><p><b>RESULTS</b>LVEF was decreased along with the prolongation of chemotherapy in the experimental group and control group. LVEDD and LVESD showed no significant changes in the experimental group, but gradually increased in the control group. After four and six cycles of chemotherapy, LVEF were (57.00 ± 5.13)% and (45.95 ± 3.68)%, respectively, in the control group, significantly lower than that of (67.00 ± 5.13)% and (57.50 ± 2.57)%, respectively, in the experimental group (P < 0.05). After six cycles of chemotherapy, LVEDD and LVESD were (50.00 ± 10.48) mm and (35.01 ± 2.99) mm, respectively, in the control group, significantly higher than those before chemotherapy (P < 0.05) and experimental group (P < 0.001). The rate of ST segment and T wave abnormalities was 80.0% in the control group after six cycles of chemotherapy, significantly higher than that of 25.0% after four cycles of chemotherapy (P = 0.001) and 10.0% after two cycles of chemotherapy (P < 0.001). The reduction of QRS voltage, arrhythmia and abnormal troponin were 55.0%, 45.0% and 45.0%, respectively, in the control group, significantly higher than those in the experimental group (20.0%, P < 0.05), (10.0%, P = 0.010) and (10.0%, P < 0.05), respectively. The rate of abnormal expression of troponin was 45.0% in the control group, significantly higher than the 10.0% in the experimental group (P < 0.05).</p><p><b>CONCLUSIONS</b>The use of low-dose carvedilol combined with candesartan can reduce the acute and chronic cardiotoxicity of anthracycline drugs, and with tolerable toxicities. This may provide a new approach to prevent cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer.</p>

Relation of lymphatic microvessel density detected by monoclonal antibody D2-40 with VEGF-C expression in breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the relationship of lymphatic micovessel density (LMVD) detected by monoclonal antibody D2-40) with the VEGF-C expression in human breast cancer.</p><p><b>METHODS</b>Tissue samples of 102 breast cancers, 25 breast fibroadenomas and 10 normal breasts were collected. Immunohistochemical staining was used to detected the lymphatic micovessels with monoclonal antibody D2-40. The expression of VEGF-C was detect by SP immunohistochemistry, and VEGF-C mRNA by hybridization in situ.</p><p><b>RESULTS</b>In 102 breast cancers, the positive rate of D2-40 was 76.5% (78/102), higher than that in the breast fibroadenomas. LMVD in the periphery of breast cancer was 30.1 lymphatic microvessels per x 100 field of vision, which was significantly higher than that in the central area of the tumors (P = 0.000). The LMVD in the periphery of the breast cancers was correlated with the number of metastatic lymph nodes (r = 0.964, P < 0.01). The positive rates of VEGF-C protein and mRNA were 55.9% (57/102) and 59.8% (61/102), respectively, significantly higher than that in the breast fiberoadenomas and normal breast tissues (chi2 = 11.653, P = 0.003; chi2 = 10.345, P = 0.006), and were significantly correlated with the status of lymph node metastasis, clinical stage and the expressions of c-erbB-2 and p53 protein (P < 0.05). Both of VEGF-C protein and mRNA were significantly correlated with LMVD detected by D2-40 (P < 0.05), especially with the LMVD in the periphery of breast cancers (P < 0.05).</p><p><b>CONCLUSION</b>The monoclonal antibody D240 can be used to detect the lymphatic endothelium in human breast cancer. The lymphatic microvessel density in the periphery of breast cancer is correlated with the lymph node metastasis and expression of VEGF-C. Therefore, VEGF-C may play a significant role in the lymphangiogenesis leading to metastasis of breast cancer.</p>