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Timing of trastuzumab and risk of cardiac dysfunction in HER2 positive early breast cancer patients.

Breast cancer is the most common malignant tumor in females in the world. Age is signifi cant risk factor and incidence increases rapidly after age of 35. Approximately one fourth of patients with breast cancer have tumors that overexpress HER2 protein or amplify the HER2/neu gene.Trastuzumab is a recombinant humanized monoclonal antibody that binds to a specific extracellular growth factor, human epidermal growth factor type 2 HER 2-neu or ErbB2, tyrosine kinase receptor responsible for alterations in cellular metabolism and growth.Clinical studies have shown that trastuzumab given concurrently or following adjuvant chemotherapy improves disease- free survival (DFS) and overal survival (OS) in early- stage HER-2 positive breast cancer. HERA study (Herceptin in Adjuvant breast cancer) showed that one of fifty women treated with trastuzumab adjuvantly developes congestive heart failure during treatment.Mechanisms of trastuzumab induced cardiac dysfunction are not clear yet. Studies have shown that differences in timing of trastuzumab after chemotherapy an ddifferences in total dose of anthracyclines can explain differences in incidence of cardiac dysfunction. The aim of our study was to determine incidence of trastuzumab induced cardiac dysfunction in patients with HER2 positive early breast cancer and impact of time interval between administration of chemotherapy and trastuzumab on prevalence of cardiac dysfunction. Follow up included 140 patients with early HER2 positive breast cancer treated with trastuzumab adjuvantly. Seventeen patients developed symptomatic cardiac dysfunction (12.1%) of which 6 developed severe congestive heart failure NYHA III/IV(4.2%) and 11 moderate NYHA II/III (7.9%).Patients who started trastuzumab therapy 11 to 20 days after finishing chemotherapy had 11% incidence of symptomatic heart failure, same as those patients who started trastuzumab 26 to 35 days after chemotherapy. There were no cardiac events if treatment was started 35 days after chemotherapy. Highest incidence of congestive heart failure was registered when trastuzumab was applied 21 to 25 days after adjuvant chemotherapy (22%). Time interval between cessation of adjuvant chemotherapy and fi rst trastuzumab application has a signifi cant impact on prevalence of trastuzumab induced cardiac dysfunction.

breast cancer ; trastuzumab ; cardiac dysfunction ; adjuvant chemotherapy ; anthracyclines

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