HER2 positive breast cancer: is there a preventive role of cardioprotective drugs?
Authors: Martins De Carvalho M , Pinto R A , Proenca T , Costa I , Torres S , Resende C X , Grilo P D , Amador A F , Costa C , Calvao J , Sousa C , Paiva M , Macedo F , Marques C , Cabrita A 
Published: October 2021

Abstract

Introduction
In patients with breast cancer, anti-HER2-targeted therapies (AHT) are highly associated with cardiotoxicity (CT), being the main reason for treatment interruption in patients receiving adjuvant trastuzumab. Guidelines recommend regular left ventricular ejection fraction (LVEF) assessments and CT's management with cardioprotective drugs (CPD). However, while secondary prevention has already entered clinical practice, primary prevention is still in the research domain. Our aim was to evaluate risk of CT and the role of CPD in a subset of breast cancer patients treated with AHT.

Methods
We retrospectively analyzed a population of breast cancer female patients treated with AHT referred to Cardio-oncology consultation at a tertiary center from January 2017 to March 2020. All patients were evaluated with echocardiogram before treatment initiation and at least at 3, 6, 9 and 12-months. CT was defined as LVEF under 50% or decline of at least 10% in LVEF during follow-up. As CPD we considered renin-angiotensin-aldosterone system inhibitors and beta-blockers.

Results
A total of 85 patients were included with mean age of 52.4±10.2 year-old. Concerning cardiovascular risk factors 11.8% had diabetes, 32.9% dyslipidaemia, 29.4% hypertension and 22.4% were smokers or previous smokers; most patients had a high or very-high CT risk score (98.8% with score ≥5). Besides AHT, 68.2% and 80% were also on anthracyclines and radiotherapy, respectively. Patients were followed for a median follow-up of 16 months. At baseline, mean high sensitivity troponin I was 3.9 ng/L, mean LVEF was 63.1% and mean global longitudinal strain was −19.7, with all patients having normal cardiac function. During follow-up, 15.7% developed CT with a higher prevalence in patients concomitantly on anthracyclines (19.6% vs 7.4%, p=0.151). CPD was initiated or titrated in 84.6% of patients and 30.8% needed to suspend AHT; overall 92.3% of CT patients recovered. Unlike AHT suspension, CPD initiation after CT was associated with a higher rate of cardiac function recovery (100.0% vs 50.0%, p=0.020). When comparing patients already medicated with CPD before cancer treatment (41.7%) to those naïve of CPD, the first group presented a significative lower incidence of CT [2.9% vs 25.0%, p=0.006, OR=0.09 (95% CI 0.01 – 0.72)]. When analysed all sample (with or without CT), patients already on CPD also presented a higher LVEF at 6 months follow-up (62.5% vs 59.2%, t(69)=−2.4, p=0.017 at 6 months), despite a non-significative lower LVEF at baseline (62.3% vs 63.6%, p=0.139). Medication with statins before chemotherapy didn't reduce the risk of CT.

Conclusion
Pre-treatment with CPD was significantly associated with a lower prevalence of CT and a higher LVEF at 6-months follow-up. CPD initiation after CT was associated with cardiac function recovery. These results highlights the importance of cardiac evaluation in HER2+ patients and strengthen the primary prevention field in these patients.

Funding Acknowledgement
Type of funding sources: None.