Incidence of Cardiotoxicity and Validation of the Heart Failure Association- International Cardio-Oncology Society risk stratification Tool in Patients Treated with Trastuzumab for HER2-Positive Early Breast Cancer.

Abstract

PurposeTrastuzumab improves survival in patients with HER2+ early breast cancer. However, cardiotoxicity remains a concern, particularly in the curative setting, and there are limited data on its incidence outside of clinical trials. We retrospectively evaluated the cardiotoxicity rates (left ventricular ejection fraction [LVEF] decline, congestive heart failure [CHF], cardiac death or trastuzumab discontinuation) and assessed the performance of a proposed model to predict cardiotoxicity in routine clinical practice.MethodsPatients receiving curative trastuzumab between 2011-2018 were identified. Demographics, treatments, assessments and toxicities were recorded. Fisher’s exact test, chi-squared and logistic regression were used.Results931 patients were included in the analysis. Median age was 54 years (range 24-83) and Charlson comorbidity index 0 (0-6), with 195 patients (20.9%) aged 65 or older. 228 (24.5%) were smokers. Anthracyclines were given in 608 (65.3%). Median number of trastuzumab doses was 18 (1-18). The HFA-ICOS cardiovascular risk was low in 401 patients (43.1%), medium in 454 (48.8%), high in 70 (7.5%) and very high in 6 (0.6%).Overall, 155 (16.6%) patients experienced cardiotoxicity: LVEF decline≥10% in 141 (15.1%), falling below 50% in 55 (5.9%), CHF NYHA class II in 42 (4.5%) and class III-IV in 5 (0.5%) and discontinuation due to cardiac reasons in 35 (3.8%). No deaths were observed.Cardiotoxicity rates increased with HFA-ICOS score (14.0% low, 16.7% medium, 30.3% high/very high; p=0.002). ConclusionsCardiotoxicity was relatively common (16.6%), but symptomatic heart failure on trastuzumab was rare in our cohort. The HFA-ICOS score identifies patients at high risk of cardiotoxicity

Involvement of kallikrein‐PAR2‐proinflammatory pathway in severe trastuzumab‐induced cardiotoxicity

“…The known risks of developing cardiotoxicity include age, a history of anthracycline treatment, and cardiovascular events. 18,19 However, unpredictable cases of cardiotoxicity also occur in clinical practice, in patients with none or few risk factors. Some genomewide association studies have explored the hypothesis that Tmabinduced cardiotoxicity might occur in patients with a particular genetic background in addition to the aforementioned acquired risk factors, and several SNPs have been identified.…”

“…The known risks of developing cardiotoxicity include age, a history of anthracycline treatment, and cardiovascular events 18,19 . However, unpredictable cases of cardiotoxicity also occur in clinical practice, in patients with none or few risk factors.…”

Cardiotoxicity of Chemotherapeutic Drugs: An Update and Future Perspectives

“…39 When trastuzumab is used in combination with anthracycline chemotherapy, the incidence of cardiotoxicity is known to be higher. 40…”

Baseline cardiac function checkup in patients with gastric or breast cancer receiving trastuzumab or anthracyclines

“…26 This tool has also been validated in patients with early BC who are receiving trastuzumab. 27 In these studies, several risk factors for cardiotoxicity induced by anthracyclines and trastuzumab were identified, including older age, low baseline LVEF, and previous cardiotoxic cancer treatment. This tool exhibited low sensitivity (14.8%) and high specificity (93.2%), 27 implying that risk stratification would help identify high-risk patients and encourage physicians to implement strict guidelinebased cardiac function follow-up.…”