Key result
Adding anthracycline/cyclophosphamide to HER2-directed therapy linked to ~43% absolute increase in RHI deterioration.
Why the study?
The study was conducted to evaluate how HER2-directed therapy affects peripheral vasoreactivity, its correlation with cardiac function changes, and the additive effects of anthracycline/cyclophosphamide therapy and baseline cardiovascular risk.
Does the addition of anthracycline/cyclophosphamide to HER2-directed therapy worsen peripheral vascular and cardiac function in women with newly diagnosed breast cancer?
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.
Answers are grounded in this paper and cite their sources.
Anthracycline addition was associated with greater endothelial dysfunction; hypothesis-generating for regimen-specific vascular monitoring in breast cancer.
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.
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Hazim et al. (2023) 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.
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