Study procedures: blood sample collection
death, tumor
BLOOD, TUMOR
For patients in the adjuvant group, clinical data were collected at baseline after surgery and before initiation of chemotherapy. Patients in the neoadjuvant group were assessed for baseline data before initiation of chemotherapy and before surgery. Blood sample collection included an assessment of high sensitivity troponin-I (hsTnI), N-terminal pro B-type natriuretic peptide (NT-proBNP) and peripheral blood mononuclear cells (PBMCs) analysis for mitochondrial respiration and cell death. Echocardiogram was performed to assess baseline cardiac function. Blood for PBMCs analysis was repeated at 2nd cycle, 4th cycle, and 6th cycle (for 6FAC regimen) immediately after complete infusion of chemotherapy in each cycle. Cardiac biomarkers were assessed at 4th cycle, 6th cycle (for 6FAC regimen) immediately after complete infusion of chemotherapy in each cycle and were repeated at 2-week and 3-month, 6-month, 9-month and 12-month after completion of doxorubicin therapy. Highest level of hsTnI between the final cycle and at 2-week after doxorubicin was used for primary outcome analysis. Patients were re-evaluated with echocardiogram at 2 weeks, 3-month, 6-month, 9-month and 12-month after completion of doxorubicin therapy. Patients implanted with breast silicone were excluded from echocardiographic analysis. After completion of doxorubicin treatment, some patients may need further treatment with paclitaxel or trastuzumab, which depended on their tumor status. However, the primary outcome of hsTnI level was measured prior to the administration of paclitaxel and trastuzumab. The study protocols are illustrated in Fig. Trial protocol. Baseline evaluation included clinical data collection, echocardiogram, and blood test for biomarkers and PBMCs analysis. Blood samples were obtained at baseline, at 2nd cycle, 4th cycle, 2-week post-DOX and every 3-month until 12-month post-DOX. Echocardiogram was repeated at 2-week post-DOX and every 3-month until 12-month post-DOX. 