Assessing heart function in recently-diagnosed breast cancer patients
Research type
Research Study
Full title
Longitudinal Characterisation of Cardiac Function in recently-diagnosed breast cancer patients
IRAS ID
188676
Contact name
Erifyli Piastopoulou
Contact email
Clinicaltrials.gov Identifier
TBC, TBC
Duration of Study in the UK
1 years, 4 months, 31 days
Research summary
Research Summary
We will investigate the influence of systemic adjuvant therapy (SAT: chemotherapy +/- trastuzumab) on heart function/rhythm and cardio-respiratory fitness (CRF) in recently diagnosed breast cancer patients. In some patients, SAT damages the heart (so-called ‘cardiotoxicity’) and this can have a serious impact on quality of life and survival. The conventional methods for assessing heart function (specifically the ‘ejection fraction’) are nuclear medicine (MUGA) and echocardiography. These are performed before and after chemotherapy in patients at higher risk of cardiotoxicity (those who need anthracyclines and have risk factors for cardiotoxicity) and in all patients receiving trastuzumab (who receive further assessments at 3-4 month intervals until completion of treatment). It is not practical or cost-effective to scan more frequently using MUGA (the method used in ABMU) but we will investigate whether an alternative method (Impedance Cardiography, ICG) could be used instead. This technique would allow more frequent monitoring throughout treatment because it is inexpensive, does not involve ionising radiation and is easy to perform.
Anticancer therapies can also lead to heart rhythm abnormalities and cardiac autonomic dysfunction, but these are not routinely monitored in breast cancer patients. We will quantify the impact of SAT on these temporal ECG variables. We will also characterise (for the first time) changes in body composition, CRF and physical activity that occur during and following SAT, and we will investigate cause-effect relationships between these using cardiopulmonary exercise testing (fitness), accelerometry (activity levels) and DEXA radiography (body composition). The monitoring techniques used in routine care cannot detect the variety of cardiorespiratory changes that might occur, and our study will lead to better diagnosis of cardiorespiratory status in the future. Eligible participants: women aged >18 years with early invasive breast cancer (stage I-III), treated surgically, due to start SAT (chemotherapy +/- trastuzumab) and WHO performance status 0-2.
Summary of Results
Background: In some patients, breast cancer treatment damages the heart (so-called ‘cardiotoxicity’) and this can have a serious impact on the patient’s quality of life and overall survival. It has also been suggested that anticancer therapies may lead to reduced cardiac autonomic function, clinically reflected by an increase in heart rate and a reduction in heart rate variability. Evidence also indicates that cardiorespiratory fitness (as measured by the rate of oxygen uptake in the body) is impaired in breast cancer patients compared to healthy controls, even several years following the completion of treatment. However, there is a lack of information in the literature regarding the extent and time-course of changes in cardiac function, cardiac rhythm and cardiorespiratory performance (or ‘fitness’) in these patients. Furthermore, current methods (MUGA, echocardiography) used in clinical practice to detect abnormal cardiac changes as a result of treatment suffer from important limitations. Use of alternative techniques that would offer safe, inexpensive and non-invasive cardiac function assessment in this population would be highly advantageous. The aim of this study was to: 1) Characterise the time course of changes in cardiac function, cardiac autonomic nervous system function and cardiorespiratory fitness, and 2) Compare impedance cardiography (ICG) and cardiac magnetic resonance imaging (CMR) in quantifying stroke volume (SV), cardiac output (CO) and end-diastolic volume (EDV) in this population.
Methods: Sixteen early-stage breast cancer patients, scheduled to undergo chemotherapy alone (6 cycles) or with anti-HER2 (Human Epidermal growth factor Receptor 2) targeted therapy (given concurrently with chemotherapy; 18 cycles), were recruited from two local health boards. Patients underwent ICG assessment and concurrent ECG assessment, CMR imaging and cardiorespiratory fitness assessment at three different time-points (before treatment, immediately after chemotherapy, and four months after chemotherapy). ICG and ECG assessments were performed under different physiological and physical states (i.e. supine, sitting, standing, moderate-intensity exercise and seated recovery). Bland–Altman analysis was used to quantify the accuracy and precision of ICG (relative to CMR) in estimating absolute values of SV, CO and EDV. Four methods (concordance rate, polar concordance rate, clinical concordance rate and trend interchangeability rate) were also used to assess ICG performance in tracking changes in these variables.
Results: Overall, ICG demonstrated poor agreement with CMR in quantifying absolute and serial SV, CO and EDV measurements. Although right ventricular function was not altered during or after treatment, clinically significant changes were observed in left ventricular function and structure. Significant reductions were also observed in various ICG-derived variables during and after treatment when examined in multiple physiological and physical states, potentially indicating a detrimental treatment-induced effect. Cardiac autonomic function assessment revealed significant changes in heart rate variability (HRV). Furthermore, although maximal rate of oxygen uptake was significantly reduced immediately after chemotherapy and then improved four months after completion of chemotherapy, an appreciable number of patients showed an abnormal cardiovascular response to maximal exercise testing.
Conclusion: Treatment substantially influenced several measures of cardiovascular function, cardiac autonomic function and cardiorespiratory function in breast cancer patients. Whilst ICG cannot be used interchangeably with CMR, it has potential value in assessing cardiovascular function more comprehensively as it can be used across multiple physical states.
REC name
Wales REC 6
REC reference
16/WA/0183
Date of REC Opinion
8 Jul 2016
REC opinion
Further Information Favourable Opinion