Combination therapy with anthracycline/cyclophosphamide and HER2-directed therapy led to a greater deterioration in reactive hyperaemia index than HER2-directed therapy alone (65% vs 22%; P=0.003).
Cohort (n=47)
No
Does the addition of anthracycline/cyclophosphamide to HER2-directed therapy worsen peripheral vascular and cardiac function in women with newly diagnosed breast cancer?
The addition of anthracycline/cyclophosphamide to HER2-directed therapy in breast cancer patients is associated with early declines in both peripheral vascular and cardiac function compared to HER2-directed therapy alone.
Absolute Event Rate: 65% vs 22%
p-value: p=0.003
Abstract Aims The objective of this study was to assess the effect of HER2-directed therapy (HER2-Tx) on peripheral vasoreactivity and its correlation with cardiac function changes and the additive effects of anthracycline/cyclophosphamide (AC) therapy and baseline cardiovascular risk. Methods and results Single-centre, prospective cohort study of women with newly diagnosed stage 1–3 HER2-positive breast cancer undergoing HER2-Tx +/− AC. All participants underwent baseline and 3-monthly evaluations with Endo-Peripheral Arterial Tonometry (Endo-PAT), vascular biomarkers C-type natriuretic peptide (CNP) and neuregulin-1 beta (NRG-1β), and echocardiography. Cardiotoxicity was defined as a decrease in the left ventricular ejection fraction (LVEF) of 10% to a value 53%. Of the 47 patients enrolled, 20 (43%) received AC in addition to HER2-Tx. Deterioration of reactive hyperaemia index (RHI) on Endo-PAT by ≥20% was more common in patients receiving HER-Tx plus AC than HER2-Tx alone (65% vs. 22%; P = 0.003). A decrease in CNP and log NRG-1β levels by 1 standard deviation did not differ significantly between the AC and non-AC groups (CNP: 20.0% vs. 7.4%; P = 0.20 and NRG-1β: 15% vs. 11%; P = 0.69) nor did GLS (35% vs. 37%; P = 0.89). Patients treated with AC had a significantly lower 3D LVEF than non-AC recipients as early as 3 months after exposure (mean 59.3% (SD 3) vs. 63.8% (SD 4); P = 0.02). Reactive hyperaemia index and GLS were the only parameters correlating with LVEF change. Conclusion Combination therapy with AC, but not HER2-Tx alone, leads to a decline in peripheral vascular and cardiac function. Larger studies will need to define more precisely the causal correlation between vascular and cardiac function changes in cancer patients.
Hazim et al. (Fri,) conducted a cohort in newly diagnosed stage 1-3 HER2-positive breast cancer (n=47). HER2-directed therapy plus anthracycline/cyclophosphamide vs. HER2-directed therapy alone was evaluated on Deterioration of reactive hyperaemia index (RHI) on Endo-PAT by ≥20% (p=0.003). Combination therapy with anthracycline/cyclophosphamide and HER2-directed therapy led to a greater deterioration in reactive hyperaemia index than HER2-directed therapy alone (65% vs 22%; P=0.003).