Abstract
Background
Anti-HER2 targeted therapy has significantly reduced the recurrence and death of HER2-overexpressing breast cancer patients, but might lead to cardiotoxicity. Some patients with normal myocardial function may suffer from subclinical myocardial dysfunction after anti-HER2 targeted therapy. We sought to evaluate earlier the subclinical myocardial dysfunction in breast cancer patients after single or dual anti-HER2 targeted therapy, and identify the risk factors related to subclinical myocardiotoxicity.
Methods
In our study, 40 breast cancer patients after single anti-HER2 targeted therapy, and 40 breast cancer patients after dual anti-HER2 targeted therapy were enrolled. Global longitudinal strain (GLS) was measured through echocardiography.
Results
Seven patients in single anti-HER2 therapy group and eight patients in dual anti-HER2 therapy group had GLS lower than − 18%, suggesting subclinical myocardial dysfunction, but no difference between these two groups. Furthermore, we found that increased BMI was associated with reduction of GLS in breast cancer patients after anti-HER2 targeted therapy. Increased BMI (OR 2.683; 95% CI 1.225–5.879) was a risk factor of subclinical cardiotoxicity in dual anti-HER2 targeted therapy group. In addition, the patients with BMI ≥ 25 were more prone to have subclinical myocardial dysfunction in dual anti-HER2 therapy group compared with those with BMI ≥ 25 in single anti-HER2 therapy group.
Conclusion
Our results indicate dual anti-HER2 therapy does not increase the risk of subclinical myocardial dysfunction for breast cancer patients, compared with single anti-HER2 therapy. Patients with BMI ≥ 25 are more prone to have subclinical cardiotoxicity after dual anti-HER2 therapy than after single anti-HER2 therapy. Weight reduction should be the major measure to prevent subclinical myocardial dysfunction for these patients.
Keywords: Breast cancer, Cardiotoxicity, Anti-HER2 targeted therapy
Introduction
Breast cancer is the most common malignant tumor in females [1]. The previous studies showed that 20–25% of breast cancer patients had an overexpression of human epidermal growth factor receptor 2 (HER2) which indicated a poor prognosis of the patients [2]. Trastuzumab is a humanized monoclonal antibody, which can effectively inhibit the overexpression of HER2 through ligand-independent isomerization [3]. Therefore, Trastuzumab, which is regarded as single anti-HER2 therapy, has been widely used to treat the breast cancer patients with overexpression of HER2 in the past 2 decades. In addition, pertuzumab is a new generation of humanized monoclonal antibody of HER2. The combination of trastuzumab and pertuzumab (dual anti-HER2 targeted therapy), which has an enhanced blocking effect on signaling pathway, could effectively improve the clinical outcome of patients with HER2 over-expressed breast cancer, reducing the risk of both recurrence and death [4, 5].
Meanwhile, previous studies showed that anti-HER2 therapy might cause the death of myocytes though blocking HER2 and increasing reactive oxygen products, thereby increasing the risk of cardiotoxicity [6]. The more complete blockade of HER2 by dual anti-HER2 therapy could lead to an increased apoptosis of myocardial cells. The European Society of Cardiology had defined cancer therapy-related cardiac dysfunction (CTRCD), which was the reduction of left ventricular ejection fraction (LVEF) over 10% or decrease of LVEF to a value below 50% [7]. Although some studies found that dual anti-HER2 therapy showed no increase of cardiotoxicity compared with trastuzumab alone [8], in some specific populations, such as patients with coronary heart disease, dual anti-HER2 therapy caused a greater decrease in LVEF compared with the single anti-HER2 therapy [9].
Previous studies routinely evaluated the cardiotoxicity through measurement of LVEF by echocardiography. However, a decrease of LVEF might occur after severe damage of myocardium. And at that stage, myocardium had suffered from an irreversible myocardial injury [10]. Measurement of GLS (global longitudinal strain) using two-dimensional speckle tracking echocardiography (STE) is a novel way to detect early change of left ventricular function, thus predicting the occurrence of CRTCD [11]. However, due to lack of attention to GLS, this method is not routinely used in breast cancer patients. In our study, we aim to evaluate the subclinical myocardial dysfunction by GLS in breast cancer patients after anti-HER2 therapy.
Obesity is a risk factor of many diseases including tumors [12]. Several studies have shown that a higher BMI is associated with an increased risk of the occurrence, recurrence and metastasis of the breast cancer [13]. In addition, patients with higher BMI have an increased risk of cardiovascular disease, suggesting that these patients may be prone to cardiotoxicity after tumor therapy.
Rare studies focused on the subclinical myocardial injury in breast cancer patients after single and dual anti-HER2 targeted therapy. Therefore, our study aimed to compare the rate of subclinical myocardial dysfunction between single and dual anti-HER2 targeted therapy, and identify the related risk factors, in order to provide a rationale for the prevention of the subclinical cardiotoxicity in these patients.
Methods
Study design and population
In our study, 40 breast cancer patients after single anti-HER2 targeted therapy and 40 breast cancer patients after dual anti-HER2 targeted therapy were consecutively enrolled in Breast Center of Peking University People’s Hospital between February 2023 to October 2023 (Fig. 1). The inclusion criteria were: (1) patients were diagnosed with stage I-III breast cancer; (2) patients had completed AC-TH(P) therapy including completion of 1-year single anti-HER2 targeted therapy, which was trastuzumab, or 1-year dual anti-HER2 targeted therapy, which was a combination of trastuzumab and pertuzumab. During the therapy, cardiac monitoring was conducted every 3 months; (3) Single or dual anti-HER2 targeted therapy ended within 12 months. (4) patients had body weight change of less than 10% in the past 2 years. The exclusion criteria in our study were patients with heart failure (LVEF < 50%), heart-, liver- or kidney-related diseases. Troponin I (TnI) and serum type B natriuretic peptide were collected in this study. Baseline characteristics of the breast cancer patients were also collected. The previous therapeutic regime in these patients is AC-TH(P) according to the NCCN guidelines. AC (Anthracycline + Cyclophosphamide) was used for 4 cycles first, followed by paclitaxel or docetaxel for 4 cycles and single or dual anti-HER2 targeted therapy for 1 year. In the therapeutic regime, anthracycline was not used simultaneously with anti-HER2 targeted therapy. The study protocol was approved by the Ethics Committee of Peking University People’s Hospital. The informed consent form was signed by all the patients.
Fig. 1.
The design of our study which included 40 patients within 1 year after completion of single anti-HER2 targeted therapy and 40 patients after dual anti-HER2 targeted therapy
Image acquisition
Transthoracic echocardiography and contrast enhanced echocardiography were performed using GE95. All the image acquisition and analysis were done by the same technician and the same cardiologist. Traditional echocardiography was performed in each patient. LVEF was assessed by the two-plane Simpson method using left ventricular opacification (LVO) through contrast enhanced echocardiography, which had an increased accuracy compared to traditional echocardiography. GLS was calculated using two-dimensional speckle tracking echocardiography. The image of left ventricular apical 4 chamber, 2 chamber and 3 chamber were collected for 5 consecutive cardiac cycles using high frame rate (> 50 frames/s). Optimization of the gain, compress and time-gain compensation controls was performed to obtain the clear appearance of the left ventricle. Q-analysis (EchoPAC, GE Healthcare) was used to evaluate 2D strain. The software sketched the endocardial and epicardial boundary as a region of interest, and the boundary tracking was optimized by manual corrections. GLS and the bovine eye map of 17 left ventricular segments were automatically provided by the system.
Statistical analysis
SPSS 20.0 software was used to perform the analysis. Continuous variables were expressed by mean ± standard deviation. Categorical variables were represented by percentage of patients in each group. Comparison of continuous variables was made using independent sample t-test. Comparison of categorical variables was performed using Person’s chi-square test. Multiple linear regression was performed to analyze the risk factors related to GLS. Logistic regression was performed to analyze the risk factors related to subclinical cardiotoxicity. P < 0.05 was considered to have statistical significance.
Results
Baseline characteristics
Baseline characteristics of the 40 breast cancer patients after single anti-HER2 targeted therapy and 40 breast cancer patients after dual anti-HER2 targeted therapy were shown in Table 1. There were no significant differences in age, BMI, cardiovascular risk factors, vital sign, and other therapies between single and dual anti-HER2 targeted therapy group. All the patients had the normal TnI and BNP levels (Table 2). There were no significant differences between two groups.
Table 1.
Baseline characteristics of breast cancer patients after anti-HER2-tageted therapy
| Trastuzumab (n = 40) |
Trastuzumab + pertuzumab (n = 40) |
P value | |
|---|---|---|---|
| Demographics | |||
| Age (years) | 54.0 ± 9.2 | 53.7 ± 10.3 | 0.654 |
| BMI (kg/m2) | 24.8 ± 3.1 | 24.5 ± 3.4 | 0.538 |
| Cardiovascular risk factors | |||
| Hypertension | 3(7.5%) | 4(10%) | 0.462 |
| Diabetes mellitus | 2(5%) | 3(7.5%) | 0.389 |
| Dyslipidemia | 2(5%) | 3(7.5%) | 0.389 |
| Coronary heart disease | 0 | 0 | - |
| Vital sign | |||
| Systolic blood pressure (mmHg) | 123.3 ± 13.6 | 121.5 ± 15.3 | 0.674 |
| Diastolic blood pressure (mmHg) | 77.1 ± 9.8 | 76.8 ± 8.8 | 0.728 |
| Therapies | |||
| Anthracycline use | 30(75%) | 20(50%) | 0.357 |
| Left-side radiotherapy | 12(30%) | 15(37.5%) | 0.433 |
Table 2.
Troponin I and BNP of single and dual anti-HER2 targeted therapy group
| Trastuzumab (n = 40) |
Trastuzumab + pertuzumab (n = 40) |
P value | |
|---|---|---|---|
| Troponin I (pg/mL) | 12.1 ± 3.2 | 12.5 ± 4.1 | 0.687 |
| BNP (pg/mL) | 66.4 ± 8.3 | 63.9 ± 9.7 | 0.591 |
All the patients had normal LVEF. However, as shown in Table 3, seven patients (17.5%) in single anti-HER2 targeted therapy group had GLS that was lower than − 18%, and eight patients (20%) in dual anti-HER2 targeted therapy group had GLS that was lower than − 18%, which was the normal lower limit of GLS, indicating subclinical myocardial dysfunction in these two groups. However, there was no significant difference in the ratio of patients with abnormal GLS between the two groups. In addition, there was no significant difference in GLS and LVEF between single and dual anti-HER2 therapy group.
Table 3.
LVEF and GLS of single and dual anti-HER2 targeted therapy group
| Trastuzumab (n = 40) |
Trastuzumab + pertuzumab (n = 40) |
P value | |
|---|---|---|---|
| LVEF (%) | 62.0%±5.9% | 63.9%±4.9% | 0.516 |
| GLS (%) | −19.3%±2.8 | −19.6%±3.3% | 0.632 |
| Abnormal GLS | 7 (17.5%) | 8 (20%) | 0.365 |
We further evaluated the diastolic function related indicators including early diastolic mitral annular velocity at the interventricular septal annulus (e’), E(E wave)/e’, left atrial volume (LAV) and tricuspid regurgitation velocity (TRV), which were within normal range. We compared these indicators between the two groups. There were no significant differences in diastolic function related indicators between single and dual anti-HER2 targeted therapy groups (Table 4).
Table 4.
Diastolic function related indicator of single and dual anti-HER2 targeted therapy groups
| Trastuzumab (n = 40) |
Trastuzumab + pertuzumab (n = 40) |
P value | |
|---|---|---|---|
| e’ (cm/s) | 5.42 ± 2.32 | 5.65 ± 2.77 | 0.728 |
| E/e’ | 11.35 ± 3.29 | 10.79 ± 2.74 | 0.645 |
| LAV (ml/m2) | 30.25 ± 4.82 | 31.2 ± 5.30 | 0.383 |
| TRV (m/s) | 2.56 ± 0.32 | 2.22 ± 0.58 | 0.496 |
Association of BMI and reduction of GLS
Multivariate regression analysis was used to analyze the possible factors affecting GLS. Age, BMI, use of anthracycline, left-side radiotherapy, and anti-HER2 targeted therapy type were included. As shown in Table 5, BMI was a significant factor that affected GLS. Increase of BMI was associated with reduction of GLS.
Table 5.
Multivariate analysis of the factors associated with GLS in patients
| Factor | β | SE | P value |
|---|---|---|---|
| Age | 0.094 | 0.034 | 0.386 |
| BMI | 0.318 | 0.114 | 0.005 |
| Anthracycline | −0.053 | 0.709 | 0.639 |
| Left-side radiotherapy | −0.129 | 0.707 | 0.260 |
| Trastuzumab/Trastuzumab + pertuzumab | −0.133 | 0.759 | 0.258 |
We further analyzed whether BMI was associated with subclinical myocardial dysfunction in single anti-HER2 targeted therapy group and dual anti-HER2 targeted therapy group respectively. Multivariate regression analysis was further used to analyze the possible factors that affected GLS in single and dual anti-HER2 targeted therapy group respectively. As shown in Table 6, in single anti-HER2 targeted therapy group, BMI showed no association with GLS. Increase of age was associated with reduction of GLS. However, in dual anti-HER2 targeted therapy group, increased BMI was associated with reduction of GLS (Table 7).
Table 6.
Multivariate analysis of the factors associated with GLS in patients after single anti-HER2 targeted therapy
| Factor | β | SE | P value |
|---|---|---|---|
| Age | 0.358 | 0.045 | 0.017 |
| BMI | 0.316 | 0.112 | 0.062 |
| Anthracycline | −0.225 | 0.903 | 0.125 |
| Left-side radiotherapy | −0.199 | 0.898 | 0.171 |
Table 7.
Multivariate analysis of the factors associated with GLS in patients after dual anti-HER2 targeted therapy
| Factor | β | SE | P value |
|---|---|---|---|
| Age | 0.016 | 0.047 | 0.917 |
| BMI | 0.339 | 0.163 | 0.024 |
| Anthracycline | 0.027 | 0.918 | 0.852 |
| Left-side radiotherapy | −0.155 | 0.963 | 0.290 |
Association of BMI and subclinical myocardial dysfunction
Furthermore, we performed multivariate regression analysis to identify the factors that were related with subclinical myocardial dysfunction. GLS below − 18% was defined as subclinical cardiotoxicity according to previous studies [14, 15]. As shown in Table 8; Fig. 2, increased BMI (OR 1.417; 95% CI 1.113–1.804) was independently associated with subclinical cardiotoxicity.
Table 8.
Multivariate analysis for subclinical cardiotoxicity in patients
| β | SE | P | OR(95% CI) | |
|---|---|---|---|---|
| age | 0.081 | 0.045 | 0.072 | 1.084 (0.993–1.183) |
| BMI | 0.348 | 0.123 | 0.005 | 1.417(1.113–1.804) |
| Anthracycline | −1.383 | 0.762 | 0.070 | 0.251 (0.056–1.117) |
| Left-side radiotherapy | −0.591 | 0.722 | 0.413 | 0.554 (0.135–2.278) |
|
Trastuzumab /Trastuzumab + pertuzumab |
−0.357 | 0.808 | 0.659 | 0.700 (0.144–3.407) |
Fig. 2.
Multivariate analysis for subclinical cardiotoxicity in patients
We also investigated the possible factors that related with subclinical cardiotoxicity in the single anti-HER2 targeted therapy group and dual anti-HER2 targeted therapy group respectively. We found that BMI (OR 1.416; 95% CI 0.933–2.151) was not associated with subclinical cardiotoxicity in single anti-HER2 targeted therapy group (Table 9), whereas, BMI (OR 2.683; 95% CI 1.225–5.879) was a risk factor of subclinical cardiotoxicity in dual anti-HER2 targeted therapy group (Table 10; Fig. 3).
Table 9.
Multivariate analysis for subclinical cardiotoxicity in patients after single anti-HER2 targeted therapy
| β | SE | P | OR(95% CI) | |
|---|---|---|---|---|
| age | −0.044 | 0.067 | 0.511 | 0.957 (0.840–1.091) |
| BMI | 0.348 | 0.213 | 0.103 | 1.416(0.933–2.151) |
| Anthracycline | −0.657 | 1.117 | 0.557 | 0.518 (0.058–4.633) |
| Left-side radiotherapy | 1.585 | 1.402 | 0.258 | 4.877 (0.313–76.092) |
Table 10.
Multivariate analysis for subclinical cardiotoxicity in patients after dual anti-HER2 targeted therapy
| β | SE | P | OR(95% CI) | |
|---|---|---|---|---|
| age | 0.369 | 0.217 | 0.089 | 1.446 (0.946–2.212) |
| BMI | 0.987 | 0.400 | 0.014 | 2.683(1.225–5.879) |
| Anthracycline | −4.847 | 2.504 | 0.073 | 0.031 (0.020–1.063) |
| Left-side radiotherapy | −1.738 | 1.356 | 0.200 | 0.176 (0.012–2.508) |
Fig. 3.
Multivariate analysis for subclinical cardiotoxicity in patients after dual anti-HER2 targeted therapy
We then compared the proportion of patients that had subclinical cardiotoxicity with normal weight (BMI<25) and abnormal weight (overweight and obese, BMI ≥ 25) in these two groups. We found that the proportion was similar in patients with BMI < 25 and BMI ≥ 25 in single anti-HER2 targeted therapy group, whereas, the proportion of subclinical cardiotoxicity was increased in patients with BMI ≥ 25 compared to patients with BMI < 25 in dual anti-HER2 targeted therapy group (Fig. 4).
Fig. 4.
The proportion of subclinical cardiotoxicity of patients with normal weight and abnormal weight (overweight and obese, BMI ≥ 25) in single and dual anti-HER2 targeted therapy group
Discussion
In our study, we observed the subclinical myocardial dysfunction in breast cancer patients after anti-HER2 targeted therapy. Our main findings were as follows: (1) There was subclinical myocardial dysfunction in patients with normal LVEF after anti-HER2 targeted therapy, but no difference between single anti-HER2 targeted therapy and dual anti-HER2 targeted therapy; (2) Increased BMI was associated with reduction of GLS in breast cancer patients after anti-HER2 targeted therapy; (3) Increased BMI is the risk factor of subclinical cardiotoxicity in dual anti-HER2 targeted therapy group, not in single anti-HER2 targeted therapy group. (4) The overweight and obese (BMI ≥ 25) was independently associated with a higher rate of subclinical cardiotoxicity compared to normal weight patients in dual anti-HER2 targeted group.
In our study, we used GLS to identify the early myocardial injury of breast cancer patients after anti-HER2 targeted therapy. Measurement of LVEF is the regular way to evaluate the myocardial function in patients with cancer-related therapy. In contrast, GLS is a novel method to identify subclinical myocardial injury. It has a higher sensitivity to identify cardiotoxicity of cancer-related therapy, compared to LVEF. Cancer-related therapy may lead to impairment of just certain segments of left ventricle, which could be detected by the reduction of GLS. In this condition, LVEF may be normal because of the compensatory enhanced movement of the other segments of left ventricle [16]. In addition, several conditions, such as heart rate and preload, may affect LVEF, resulting in inaccurate assessment of myocardial function. Measurement of LVEF is performed simply through tracing, whereas GLS using two-dimensional speckle tracking echocardiography ensures a more accurate measurement of myocardial function [17]. Therefore, ASE/VACVI expert consensus recommend that GLS could be used to identify subclinical myocardial dysfunction after cancer-related therapy [18]. Previous study also showed that GLS below − 18% was a risk of cardiotoxicity and that worse GLS was associated with a higher CRTCD risk [14]. In our study, GLS was used to identify the subclinical myocardial dysfunction in patients with normal LVEF after anti-HER2 targeted therapy. Fifteen patients had GLS that was below − 18%, indicating that GLS can be an effective way to identify early subclinical myocardial dysfunction.
Our study found that increase of BMI was associated with reduction of GLS and subclinical cardiotoxicity after anti-HER2 targeted therapy. Previous study also showed that obesity was a risk factor for trastuzumab-related cardiac toxicity in elderly patients with breast cancer [19]. The mechanism that increased BMI had an effect on subclinical myocardial dysfunction could be explained by the following reasons. Firstly, overweight and obesity may promote the expression of pro-inflammatory adipokines, which could lead to a chronic inflammatory state and subsequent deterioration of myocardium [20]. Secondly, overweight and obesity was associated with production of ROS production and reduction of antioxidants, resulting in the activation of oxidative stress and sensitivity to the toxicity of the cancer-related therapy [21]. Thirdly, obesity could increase preload and afterload of the heart, resulting in a remodeling of myocardium [22]. Therefore, intervention measures for overweight and obesity, such as diet plan and exercise plan, should be carried out to reduce the risk of cardiotoxicity in patients with cancer-related therapy.
Combined administration of trastuzumab, which binds to HER2 domain IV, and pertuzumab, which binds to HER2 domain II, can achieve a more complete HER2 blocking and related pathway, resulting in an increase of reactive oxygen products and consequent death of cardiomyocyte [6]. Therefore, we found that both single and dual anti-HER2 targeted therapy group led to subclinical myocardial dysfunction. However, our study also showed that dual anti-HER2 targeted therapy did not increase subclinical cardiotoxicity compared to single anti-HER2 targeted therapy. Previous studies using LVEF as a monitor index also showed that addition of pertuzumab in anti-HER2 targeted therapy did not increase the risk of cardiac toxicity [8, 23]. A meta-analysis also found that dual anti-HER2 therapy showed no increase of cardiac toxicity compared to trastuzumab alone [24]. Besides the cardiac toxicity evaluated by LVEF shown by previous studies, our study firstly demonstrated that dual anti-HER2 therapy did not increase the risk of subclinical myocardial dysfunction identified by GLS compared to single anti-HER2 therapy. This may be explained by the mechanism that trastuzumab, but not pertuzumab, could inhibit autophagy of myocardiocytes and increase production of reactive oxygen species in cardiomyocytes [25].
Our study found that there was a reduction of GLS instead of LVEF change in obese patients, especially in obese patients after dual anti-HER2 targeted therapy. A previous study showed that clinical myocardial injury, indicated by LVEF decline, occurred mostly during anti-HER2 targeted therapy (2.6%), and rarely after completion of anti-HER2 therapy (0.7%) [26]. The conventional echocardiographic method, LVEF, is not so sensitive to identify the early myocardial dysfunction. In our study, we used GLS to detect subclinical cardiac dysfunction after completion of anti-HER2 therapy. Our study showed that LVEF was normal, but 17.5% of patients after single anti-HER2 targeted therapy and 20% of those after dual anti-HER2 therapy showed reduced GLS, indicating a subclinical myocardial dysfunction. Our study suggested that the decrease of GLS could occur earlier than the reduction of LVEF, especially in patients with cardiovascular risk factors, such as obesity. Previous studies also showed that in other diseases, such as diabetes, obstructive sleep apnea and Cushing’s syndrome, obese patients had higher rate of subclinical cardiotoxicity, indicated by a reduction of GLS, whileas LVEF was normal in these patients [27–29].
Many factors can increase the effects of trastuzumab and pertuzumab on the heart. Previous studies showed that in patients with the presence of coronary artery disease and sequential treatment with anthracycline, dual anti-HER2 targeted therapy had an increase of cardiotoxicity compared with single anti-HER2 targeted therapy [9]. Similarly, our study showed that increased BMI was associated with subclinical cardiotoxicity in dual anti-HER2 targeted therapy rather than single anti-HER2 targeted therapy. There were more patients with overweight and obesity suffering from subclinical cardiotoxicity after dual anti-HER2 therapy compared with single anti-HER2 therapy. Therefore, combination of trastuzumab and pertuzumab may increase the cardiac burden compared with trastuzumab with these risk factors. Cardiac risk assessment and cardiac monitoring is recommended for the patients during and after cancer treatment, especially in dual anti-HER2 targeted therapy.
In our study, the patients who had previously taken anthracyclines showed no increased incidence of cardiotoxicity, which can be explained by the following reasons. Firstly, in our AC-TH(P) therapy, AC was only used for 4 cycles, and A in our study was epirubicin, which was considered to be less cardiotoxic than conventional doxorubicin. The cumulative dose of epirubicin was 320-360mg/m2 in our study, which was lower than 400 mg/ m2. Previous studies showed that risk of cardiotoxicity of epirubicin developed at 806mg/m2 at age 40, 739mg/m2 at age 50 and 609mg/m2 at age 70 [26]. The average age of patients in our study was 54 years old. Therefore, the cumulative dose of epirubicin in our study was much lower than the cumulative dose that causes cardiotoxicity. Moreover, the patients with cardiovascular risk factors received dexrazoxane during 4 cycles of AC chemotherapy, which is a cardioprotective drug to prevent the cardiotoxicity of antheracycline chemotherapy and is recommended by guidelines [30]. However, dexrazoxane has no protective effect on the cardiotoxicity of anti-HER2 targeted therapy. Therefore, we did not find increased incidence of cardiotoxicity in patients who had previously taken anthracyclines in our study.
Our study had several limitations. Firstly, this was a single-center, cross-section study, although consecutive participants were enrolled in our study. Secondly, our study had a small sample size. Thirdly, we investigated patients after anti-HER2 targeted therapy within a year, resulting in a loss of data with the change of GLS during therapy. Therefore, prospective studies with large scale of people should be conducted in the future.
Conclusion
In our study, dual anti-HER2 targeted therapy did not increase the risk of subclinical myocardial dysfunction compared with single anti-HER2 targeted therapy. In dual anti-HER2 targeted therapy, patients with increased BMI were more prone to have subclinical myocardial dysfunction, compared to single anti-HER2 targeted therapy. Therefore, GLS should be routinely performed to identify subclinical myocardial injury of the patients with cancer-related therapy. And weight reduction should be the major measure to prevent subclinical myocardial dysfunction for these patients.
Acknowledgements
Not applicable.
Abbreviations
- HER2
Human epidermal growth factor receptor 2
- CTRCD
Cancer therapy-related cardiac dysfunction
- LVEF
Left ventricular ejection fraction
- GLS
Global longitudinal strain
- STE
Speckle tracking echocardiography
- TnI
Troponin I
- LVO
Left ventricular opacification
- BMI
Body mass index
- OR
Odds ratios
Authors’ contributions
TG and SW designed the research study. FZ and SW performed the research, analyzed the data and wrote the manuscript. CY, XH, DH and WJ revised the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.
Funding
This work was supported by Peking University People’s Hospital Scientific Research Development Funds (RDL2023-06) and Peking University People’s Hospital Scientific Research Development Funds (RDJP2024-30).
Data availability
Data used in this study is available from the corresponding author upon a reasonable request.
Declarations
Ethics approval and consent to participate
This study was approved by the Medical Ethics Committee of Peking University People’s Hospital (2023PHB316-001). The patients/participants provided their written informed consent to participate in this study.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Feng Zhang and Siyuan Wang contributed equally to this work.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Data used in this study is available from the corresponding author upon a reasonable request.