Frequency of Cardiac Monitoring in Patients Treated with HER2-Directed Therapies for Breast Cancer

This study will be a single-centre prospective, randomised, open-label, non-inferiority 2 by 2 factorial design trial investigating the safety of six-monthly cardiac monitoring versus standard of care three-monthly cardiac monitoring and abbreviated versus full transthoracic echocardiography (TTE) protocols in participants with HER2-positive breast cancer treated with HER2-directed therapies. There are optional extension arm and cardiac magnetic resonance imaging sub-studies available for interested participants. The duration of the primary study is 12 months. Participants will be randomised to the following arms through the course of the study: • Three-monthly surveillance TTE and full TTE protocol (control) • Three-monthly surveillance TTE and abbreviated TTE protocol • Six-monthly surveillance TTE and full TTE protocol • Six-monthly surveillance TTE and abbreviated TTE protocol The abbreviated TTE protocol used will only assess left ventricular ejection fraction which is the parameter of interest with HER2-directed therapies, whilst the full TTE protocol in the study assesses left ventricular ejection fraction, cardiac chamber size, valvular function, cardiac chamber pressures, and the pericardium. The abbreviated TTE protocol will take approximately 15 minutes to complete whilst the full TTE protocol will take approximately 45 minutes to complete. All TTE scans will be performed by qualified cardiac sonographers and images will be reported by a cardiologist. A study coordinator will coordinate and organise all TTE scans as allocated by randomisation and monitor adherence to the randomisation. Participants will be allowed to have additional TTE scans at any timepoint during the study if deemed clinically necessary by their treating clinician (either full or abbreviated protocol at the clinician's discretion). In addition to the surveillance TTEs organised as part of the randomised arms, participants will also attend a final follow up study appointment in clinic at the end of the primary study at 12 months to record adverse events and to complete a medication log. This final study appointment is estimated to take 1 hour. Participants with metastatic breast cancer who are planned to have longer than 12 months treatment with HER2-directed therapies can provide additional optional consent to participate in the optional extension arm of the study. Following the primary 12 month study period, participants who consent to the optional extension arm will continue to have either three-monthly or six-monthly surveillance TTE as originally randomised for as long as they continue to be treated with HER2-directed therapies. However, only full TTE protocols will be utilised in the extension arm of the study (ie patients will continue to have either three-monthly surveillance TTE with full TTE protocol or six-monthly surveillance TTE with full protocol). The anticipated time for each TTE scan is 45 minutes. Participants will be allowed to have additional TTE scans at any timepoint during the extension arm of the study if deemed clinically necessary by their treating clinician (full TTE protocol will be utilised). Participants will be required to attend annual study appointments in clinic during the extension arm of the study to record adverse events and to complete a medication log. This is estimated to take 1 hour. Interested participants can also consent to participate in an optional cardiac magnetic resonance imaging sub-study. Consenting participants will undergo two cardiac magnetic resonance imaging scans during the study: the first will be at time of enrolment into the study and the second at 12 months at the end of the primary study period. Cardiac magnetic resonance imaging scans will be performed by a trained radiographer and the images will be co-reported by qualified radiologists and cardiologists. Each cardiac magnetic resonance imaging scan will take approximately 15 minutes. Participants will be allowed to have additional cardiac magnetic resonance imaging scans at any timepoint during the study if deemed clinically necessary by their treating clinician. Participants who consent to the optional cardiac magnetic resonance imaging sub-study will not need to attend any additional study appointments in clinic for the sub-study.