Trastuzumab-based adjuvant chemotherapy for breast cancer: Early myocardial dysfunction detected by “speckle tracking” echocardiography (STE).

Abstract

603 Background: While anthracycline-induced type 1 cardiotoxicity is well established, type 2 trastuzumab (TZM)-induced cardiotoxicity, although less relevant and reversible, is nonetheless significant in combination with other drugs, such as taxanes (TAX). A paradigmatic clinical example of this regimen is the adjuvant setting of breast cancer patients overexpressing HER-2. In the present study we chose STE with longitudinal and circumferential Strain (S) and Strain Rate (SR), as a very sensitive tool to timely identifying left ventricular dysfunction. The biological markers of chronic inflammation/oxidative stress were also studied. Methods: A phase IV prospective non-randomized study was carried out to assess cardio-toxicity induced by the combination of epirubicin (EPI) + TAX followed by TZM administered with the conventional schedule in adjuvant setting of breast cancer patients (pts) overexpressing HER-2. Inclusion criteria: 18–70 y, histologically confirmed HER-2+ve breast cancer candidates for TZM-based 3 weekly regimen; LVEF ≥55%; ECOG PS score 0-1, no history of cardiac disease. STE parameters (longitudinal and circumferential S and SR) and chronic inflammation (IL-6 and TNF-a)/oxidative stress (reactive oxygen species) markers were assessed at baseline before TZM and after each of the subsequent 18 TZM administrations. Results: Forty pts (mean±SD age 53±10 y) were assessed up to the 8th TZM administration. A progressive reduction of longitudinal SR was observed, becoming significant from the 4th TZM dose (0.65±0.18 s-1 vs 0.81±0.16 s-1, p<0.005); a significant reduction of circumferential SR (0.60±0.15 s-1 vs 0.51 ±0.14 s-1, p< 0.01) and rotation index was also observed from the 2ndTZM dose. These changes are all indicative of myocardial systolic dysfunction. No changes of biological parameters were observed. Conclusions: The sequential administration of TZM after EPI/TAX induced an early left ventricular dysfunction detected by STE which persisted at least up to the 8th TZM administration. This study is in progress with close monitoring of pts and its ultimate goal is to select pts candidates for an effective cardio protective treatment.