Predicting and preventing cardiotoxicity after anthracycline-based breast cancer treatment

In the first study, Doctor Ilaria Papa and colleagues from the University of Brescia and Civil Hospital of Brescia (Italy) evaluated the ability of cardiac troponin-I (TnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) to predict cardiotoxicity in women with non­metastatic breast cancer starting anthracycline-based treatment. All patients underwent complete cardiological evaluation (with ECG and echocardiography) before anthracycline therapy initiation and at regular intervals until 1 year after the end of therapy; biomarkers were measured at every visit.

Of the 179 patients who completed follow-up, 30% were classed as ‘TnI+’ (TnI increase >0.04 ng/mL or >0.015 ng/mL in at least two measurements). A significant difference was observed in left ventricular ejection fraction (LVEF) between the TnI+ group and the TnI– group at 1-year follow-up (mean ± standard deviation: 60 ± 6.5% vs. 63 ± 4.1%; p=0.005). In the TnI+ group, LVEF appeared to decrease from 62 ± 4.2% at baseline to 60 ± 6.5% at 1-year follow-up, although the difference was not significant (p=0.06). In addition, 7 patients in the TnI+ group developed LV systolic dysfunction early in the first year of follow-­up (vs. 1 patient in the TnI– group).

In total, 43% of patients were classed as ‘NT­proBNP+’ (≥125 ng/L in at least two consecutive determinations). A quarter of patients (25%) in the NT­proBNP+ had more than three cardiovascular risk factors compared with 11% in the NT­proBNP– group (p=0.011). Of patients with LV systolic dysfunction, 3 out of 8 were in the NT­proBNP+ group.

Overall, the authors concluded that a combination of individual clinical risk factors and biomarkers, especially TnI, in a predictive model may allow early identification of cardiotoxicity.

In the second study, Doctor Prajith Jeyaprakash and colleagues from Nepean Hospital and the University of Sydney (Australia) performed a network meta-­analysis of randomised controlled trials (RCTs) to investigate the effect on LVEF of various prophylactic cardioprotective agents prescribed to breast cancer patients prior to anthracycline­-based chemotherapy.

Twelve RCTs (n=1,126 patients) were included in the network meta-­analysis: seven studies assessed beta­blockers alone, two assessed combinations of angiotensin-­converting enzyme inhibitor/angiotensin receptor blockers (ACEi/ARBs) and beta-blockers, with individual studies assessing ACEi/ARBs, spironolactone or rosuvastatin alone. The assessed outcome was a mean change in LVEF pre- and post-anthracycline treatment compared with placebo.

Statistically significant protection was seen in trials with beta-blockers (n=768) where LVEF was higher than placebo by 2.38% (95% confidence interval [CI] 0.52 to 4.25). A similar magnitude of LVEF preservation was seen in trials with ACEi/ARBs (2.59%; 95% CI –0.20 to 5.38), although this effect was borderline significant, which may be due to the smaller sample size (n=250). With an ACEi/ARB and beta-blocker combination (n=98), the change in LVEF was 3.67% (95% CI –0.81 to 8.15). Spironolactone showed significant preservation of LVEF by 12.80% (95% CI 3.44 to 22.16); however, this result was based on a single small study (n=83). All trials included had an intermediate or high risk of bias, with marked heterogeneity in anthracycline dosing and LVEF monitoring.

While further studies are warranted, this analysis suggests some degree of cardioprotection may be afforded by prescribing prophylactic cardioprotective agents, which may be particularly beneficial in patients at high risk of cardiotoxicity.