Anthracycline-induced Cardiotoxicity Of Breast Cancer Victims

Objective :Breast carcinoma is one of the most common cancer for female. Around 1.4 million cases will newly increase every year globally. And 60%⁸0% of them need chemotherapy. As the cornerstone of chemotherapy , anthracyclines such as epirubicin and pirarubicin have been successfully used in the treatment of a wide variety of breast tumours as well as haematopoietic and solid tumours. Many studies show:The mechanisms of cytotoxicity of anthracyclines in cancer cells are diverse including:â‘ interference with DNA unwinding of DNA strand separation and helicase activity;â‘¡direct membrane damage due to lipid oxidation;â‘¢DNA alkylation;â‘£inhibition of both DNA replication and RNA transcription;⑤DNA cross-linking. The use of anthracyclines, a family of chemotherapeutic agents with efficacy against many solid tumors has been limited by their cardiotoxicity. This cardiotoxicity manifests as a direct or indirect form. At the present stage ,free radical is thought the main reason for the cardiotoxicity .To compare the cardiotoxicity of anthracyclines between different formula different kinds and different dosage of anthracyclines , explore the cardiotoxicity of anthracyclines to provide evidences for clinical treatments.Methods: This study recruited 132 patients from July 2008 to February 2011 at Breast Center of 4th hospital of Hebei Medical University. Women with breast cancer that had been pathologically confirmed. And received chemotherapy regimen of EC (E:Epirubicin, C:Cyclophosphamide) AC(A:Pirarubicin, C:Cyclophosphamide) or TC(T:Docetaxel, C:Cyclophosphamide). Patients'characteristics between groups were well balanced, had no clinical difference. The exclusion criteria were earlier chemotherapy or radiotherapy, presence of congestive heart failure symptoms or established dilated or restrictive CMP, coronary arterial disease history, presence of moderate or severe mitral or aortic valve disease in baseline echocardiograph, any contraindication to carvedilol, bundle branch block, thyroid function disorder, or another comorbid disease. No patients were taking any of the drugs that affect cardiac function, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, diuretics, or beta- blockers. KPS≥60.Then divided them into 3 groups according to their chemotherapy formulas. And then divided the groups of EC and AC into two subgroups separately– the groups of E100C and E₇₅C(C:600mg/ m²,d1;E:100mg/ m² or 75mg/m²,d1,d2,every 3 weeks),A60C and A₅₀C(C:600mg/ m2^,d1;A:50mg/ m² or 60mg/m²,d1,d2,every 3 weeks). Evaluated the cardiotoxicity after 2 cycles and 4 cycles using ultrasound cardiogram.Criteria for cardiotoxicity .If one of the four symptoms appears, it was a sign of heart damage:1. In the stage of heart diastole, if E/A ratio﹤1;2.The thickness or movement of left ventricular wall appear abnormal;3. In the stage of heart systole, if S peak of left ventricular wall appears abnormal;4. LVEF﹤50%. Or fell more than 16%.Assessment of cardiotoxicity:â‘ Counted the numbers of patients that appear heart damage of each group. Evaluated the differences between them.â‘¡Counted the numbers of patients that appear heart damage of the groups of E₁₀₀C E₇₅C A60C and A50C separately. Evaluated the differences between E₁₀₀C and E₇₅C, then A60C and A₅₀C.Results: There were 18 patients did not take all of the 4 cycles of chemotherapy. And 4 patients were changed from E100C to E100C ,for could not tolerate disturbances of the digestive tract orâ…£marrow suppression. So a total of 110 patients were assessable for cardiotoxicity. There were 38 cases in EC arm. 36 cases in AC arm. There were 36 cases in TC arm. 20 cases in E100C arm. 18 cases in E75C arm. There were 18 cases in A60C arm. 18 cases in A50C arm. Patients'conditions of heart and lung among groups were well balanced, had no characteristics difference. In the period of chemotherapy, 5 patients had transient arrhythmia. All of the patients did not have heart failure. 1 Clinical response evaluation after 2 cycles: The result of cardiotoxicity after treatment: Of EC arm, there were 7 cases appear cardiotoxicity,18.4% (7/38). Of AC arm, there were 6 cases appear cardiotoxicity,16.7% (6/36).Of TC arm, there were 1 cases appear cardiotoxicity,2.8% (1/36 ) .Of E₁₀₀C arm, there were 4 cases appear cardiotoxicity,20% ( 4/20 ) .Of E₇₅C arm, there were 3 cases appear cardiotoxicity,16.7%(3/18).Of A₆₀C arm, there were 4 cases appear cardiotoxicity,占22.2%(4/18).Of A₅₀C arm, there were 2 cases appear cardiotoxicity,占11.1%(2/18).1.1 Compared the difference of cardiotoxicity between these arms :Compared the difference of cardiotoxicity between EC arm and AC arm,χ²=0.039,p=0.843,no statistical difference. Compared the difference of cardiotoxicity between EC arm and TC arm,χ²=3.210,p=0.073, no statistical difference. Compared the difference of cardiotoxicity between AC arm and TC arm,χ²=2.532,p=0.112,no statistical difference.1.2 Compared the difference of cardiotoxicity between the subgroups:Compared the difference of cardiotoxicity between E100C arm and E75C arm, p=0.563,There was no statistical difference between the two groups. Compared the difference of cardiotoxicity between A60C arm and A50C arm, p=0.329,There was no statistical difference between the two groups.2 Clinical response evaluation after 4 cycles:The result of cardiotoxicity after treatment: Of EC arm, there were 10 cases appear cardiotoxicity,26.3%(10/38). Of AC arm, there were 9 cases appear cardiotoxicity,25.0%(9/36). Of TC arm, there were 1 cases appear cardiotoxicity,2.8%(1/36). Of E₁₀₀C arm, there were 6 cases appear cardiotoxicity,30%(6/20). Of E₇₅C arm, there were 4 cases appear cardiotoxicity, 22.2%(4/18). Of A₆₀C arm, there were 6 cases appear cardiotoxicity,33.3%(6/18). Of A₅₀C arm, there were 3 cases appear cardiotoxicity,16.7%(3/18).2.1Compared the difference of cardiotoxicity between these arms:Compared the difference of cardiotoxicity between EC arm and AC arm,χ²=0.017,p=0.897,no statistical difference. Compared the difference of cardiotoxicity between EC arm and TC arm,χ²=8.093,p=0.004,There was statistical difference between the two groups. Compared the difference of cardiotoxicity between AC arm and TC arm, ,χ²=7.432,p=0.006.There was statistical difference between the two groups.2.2 Compared the difference of cardiotoxicity between the subgroups:Compared the difference of cardiotoxicity between E₁₀₀C arm and E₇₅C arm, ,p=0.432,There was no statistical difference between the two groups. Compared the difference of cardiotoxicity between A60C arm and A₅₀C arm, ,p=0.222,There was no statistical difference between the two groups.Conclusion:1 There is no statistical difference of cardiotoxicity among EC, AC TC A60C A50C E100C and E75C arms after 2 cycles;2 There is statistical difference of cardiotoxicity between the Anthracyclines groups and TC group after 4 cycles,EC and AC have more cardiotoxicity.3 There is no statistical difference of cardiotoxicity between A₆₀C and A₅₀C, E100C and E₇₅C.