Synopsis

Keywords: Heart, Cardiovascular, cardiotoxicity

This study explored the early cardiac changes in HER2-positive patients treated with HER2-targeted or anthracycline therapy through cardiac MRI. The results showed frequent signs of subclinical cardiotoxicity after short-term anti-cancer therapy, despite with low-moderate cardiovascular risk. T1 mapping showed the capability for early detection of pathological myocardial changes before cardiac contractile dysfunction. In HER2-positive breast cancer patients, cardiotoxicity surveillance is important and should be carefully done even with low-moderate cardiovascular risk, especially for those received anthracycline-based therapy.

Introduction

Advances in breast cancer therapy, including the development of targeted therapies, have been associated with improved prognosis in HER2-positive breast cancer patients. Despite the impressive anticancer benefit, the frequently cardiotoxicity due to cancer therapy limits their clinical use and may reduce the quality of life of cancer survivors[1]. Early identification of cardiotoxicity may play a pivotal role in avoiding treatment interruption and improving quality of life[2]. However, cardiac surveillance during cancer therapies is easily overlooked in patients with low cardiovascular risk at baseline, especially for those received non-anthracycline-based HER2-targeted therapy. In prior studies, cardiovascular risk stratification of HER2-positive breast cancer participants was not conducted at baseline. Data on early cardiac changes after a short-term anti-cancer therapy in HER2-positive breast cancer patients with low-moderate cardiovascular risk was limited. Therefore, the purpose of this study was to explore the early cardiac changes in HER2-positive patients with low-moderate cardiovascular risk through cardiac MRI. In addition, because anthracycline is a risk factor for HER2-targeted therapy, patients treated with HER2-targeted therapy and anthracycline therapy were compared for further understand the cardiotoxicity induced by HER2-targeted therapy.

Methods

We conducted a prospective cohort study of newly diagnosed HER2-positive breast cancer patients. Patients were divided into two groups according to chemotherapy regimen: HER2-targeted therapy group (treated with trastuzumab or plus pertuzumab without anthracycline) and anthracycline chemotherapy group. Cardiac MRIs (SIGNA Architect, GE Healthcare, Waukesha, WI, USA) were done before treatment and 3 months after starting, covering ventricular volumes, cardiac function, systolic myocardial strain, myocardial oedema, T1 and T2 relaxation times. The paired t test or Wilcoxon signed-rank test was used for intraindividual comparisons. The unpaired t test or Mann‒Whitney U test was used to compare variables between subgroups.

Results

Thirty-one HER2–positive breast cancer patients were evaluated (21 in the HER2-targeted therapy group, 10 in the anthracycline chemotherapy group) (Table 1). 94% patients were at low cardiovascular toxicity risk. 7 (23%) patients developed mild asymptomatic cancer therapy–related cardiac dysfunction (CTRCD) at follow-up. Patients displayed decreased left ventricular (LV) systolic function (LV ejection fraction, cardiac output index, stroke volume index and strain parameters), increased T1 and T2 relaxation times and increased LV end systolic volume index at follow-up (p<0.05) (Table 2 and Figure 1). There was no significant difference of CTRCD between anthracycline chemotherapy group and HER2-targeted therapies group. However, T1 relaxation time and heart rate was significantly higher in anthracycline chemotherapy group than in HER2-targeted therapies group at follow-up (p<0.05), while there were on significant differences regarding T1 relaxation time and heart rate between two groups at baseline (Table 3).

Discussion

This study focused on HER2-positive breast cancer patients with low-moderate cardiovascular risk. The results showed that subclinical CTRCD after a short-term therapy was frequent in this group (23%). Its overall incidence is highly variable in previous studies, ranging from 7.6% to 28%[3-6]. The majority of participants in previous studies received sequential anthracycline and trastuzumab. Thus, it can be seen that subclinical CTRCD is still frequent in HER2-positive breast cancer patients received anthracycline or HER2-targeted therapies, even with low-moderate cardiovascular risk. Consistent with previous findings[7, 8], patients showed a significant increase in T1 and T2 relaxation times at follow-up compared with baseline, which may reflect myocardial injury during cancer therapy.
Although anthracycline might be associated with a higher rate of left ventricular dysfunction[9], we found no significant differences of LV ejection fraction or strain parameters between two groups at baseline or follow-up. However, for subgroup analysis, T1 relaxation times were significantly higher in patients treated with anthracycline chemotherapy than those with HER2-targeted therapy. T1 mapping, one of the tissue-characterization techniques, enables detecting early pathological myocardial changes before cardiac contractile dysfunction.

Conclusion

For patients with HER2-positive breast cancer, Cardiac MRI scans showed frequent signs of subclinical cardiotoxicity after a short-term anti-cancer therapy, despite with low-moderate cardiovascular risk. The incidence of CTRCD was not significantly different between patients treated with non- anthracycline-based HER2-targeted therapy and anthracycline therapy, but T1 relaxation time was significantly higher after anthracycline therapy.

Acknowledgements

No acknowledgement found.

References

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