Incidence and severity of cancer-therapy-related cardiac dysfunction during contemporary breast cancer therapy in a real-world cohort

Background Cancer therapy-related cardiac dysfunction (CTRCD) is a well-known complication in breast cancer patients exposed to anthracyclines and Human Epidermal Growth Factor Receptor 2 (HER2) targeted therapy. However, the incidence of CTRCD in unselected contemporary breast cancer populations treated according to current standard-of-care regimens remains incompletely investigated. Purpose To determine the incidence of CTRCD in women receiving (neo-)adjuvant breast cancer therapy in a real-world setting. Methods In this prospective observational study, women scheduled for (neo-)adjuvant breast cancer therapy were included. Participants were categorized into three treatment regimen groups: 1) anthracycline therapy only, 2) HER2-targeted therapy only, and 3) sequential treatment with anthracycline therapy followed by HER2-targeted therapy. The primary endpoint was the incidence of CTRCD, defined according to the echocardiographic criteria included in the 2022 ESC Cardio-Oncology Guidelines (Figure 1), from baseline to 12 months after completion of scheduled therapy. Echocardiography was assessed at baseline, after completion of scheduled therapy, and 12 months thereafter. In addition, echocardiography was performed every 3 months during HER2-targeted therapy and when clinically indicated. Results In total, 515 women were included (median age: 53 years (IQR 45,64)). During follow-up, 123 (24%) developed CTRCD. Of these, 78% were classified as mild, 19% moderate, and 2% severe. The highest incidence of CTRCD was observed among participants receiving sequential anthracycline therapy (EC90 x 4) and HER2-targeted therapy (Table 1). This regimen also had the highest incidence of moderate and severe CTRCD (13%), compared with 4% in the anthracycline-only group and 1% in the HER2-only group. Overall, severe CTRCD was observed in 0.6% of all study participants. The cumulative incidence of the worst observed severity of CTRCD during follow-up, overall and by treatment regimen, is summarized in Table 1. Conclusion In this real-world breast cancer cohort, nearly one in four women developed CTRCD during follow-up; however, most cases were categorised as mild. Moderate and severe cardiac dysfunction were primarily observed in patients receiving sequential anthracycline and HER2-targeted therapy. Severe CTRCD was rare in the overall study population.