Normal cardiac biopsy results following co-administration of doxorubicin (A), Cyclophosphamide (C) and trastuzumab (H) to women with HER2 positive metastatic breast cancer

Abstract

572 Background: Trastuzumab (Herceptin, H) extends overall survival when administered with chemotherapy (CT) to patients (pts) with HER2+ metastatic breast cancer (MBC). An increase in cardiac dysfunction (CD) was seen in pts who received H + CT (paclitaxel or AC) in a phase III study. The mechanism by which H contributes to CD may include a pharmacokinetic (PK) interaction or increased cardiac sensitivity to A. This phase I study evaluated the PK of A, C, and H; the utility of CD monitoring by LVEF (echocardiogram (EC)/nuclear multigated cardiac scan (NCS)), by cardiac biopsy, and cardiac serum marker surveillance. Methods: Inclusion criteria: ages 18–60, no prior internal mammary/mediastinal XRT, no prior A or prior CT for HER2+ MBC. Pts received weekly H (4mg/kg load, 2mg/kg weekly) with AC (60/600) q3w x 6. Cardiac evaluations included physical examination, LVEF, and cardiac biopsy after C4 and/or at s/sx of CD. Biopsies were graded using published methods. Plasma for cardiac markers and PK was obtain...