Skip to main content
Download PDF

Frequency of and sex differences in cancer treatment-related cardiac dysfunction in trastuzumab-treated patients with salivary gland cancer: a retrospective cohort study

Cardio-Oncology volume 10, Article number: 44 (2024) Cite this article

Abstract

Background

Trastuzumab treatment for salivary gland, gastric, and breast cancer commonly causes cancer treatment-related cardiac dysfunction (CTRCD). CTRCD incidence by sex has not been well studied.

Methods

This retrospective cohort study investigated frequency of and sex differences in CTRCD in patients with salivary gland cancer treated with trastuzumab at our hospital from April 2017 to March 2022. All patients underwent echocardiography at baseline and after the first, third, and sixth trastuzumab courses. We measured changes in global and regional longitudinal strain (LS) after trastuzumab administration. CTRCD was defined by left ventricular ejection fraction (LVEF) or global LS (GLS). The results were compared by sex.

Results

We recorded clinical data of 49 patients (median age [IQR], 65 [55–71] years; males [75.5%]). The median follow-up period after the sixth trastuzumab course was 120 (111–128) days. One female patient and no male patient had CTRCD defined by LVEF, and two female patients (16.7%) and seven male patients (18.9%) had CTRCD, defined by GLS. The Kaplan–Meier curves showed no significant difference in CTRCD frequency, defined by GLS (log-rank, p = 0.88), between female and male patients. In the univariate analysis, sex was not associated with CTRCD, defined by GLS. A significant difference in apical LS was observed between baseline and the third follow-up results of male patients.

Conclusions

In this study, CTRCD incidence was not significantly different between male and female patients with salivary gland cancer treated with trastuzumab. Although most previous studies have looked at female patients with breast cancer, a male patient may be found to be at similar risk of myocardial damage.

Introduction

Trastuzumab, a human epidermal growth factor receptor 2 (HER2)-targeted therapy, is a major cause of cancer therapy-related cardiac dysfunction (CTRCD), with decreased left ventricular ejection fraction (LVEF) in 25% of cases and symptomatic heart failure in 0.8–4.0% of cases [1,2,3,4]. Trastuzumab has been mainly used for treating HER2-positive breast cancer and indicated for treating HER2-positive gastric cancer. However, it is less commonly used for treating advanced metastatic or recurrent gastric cancer [5] and is less often evaluated for its associated cardiotoxicity. Trastuzumab-associated cardiotoxicity has mostly been reported in patients with breast cancer and more frequently in those with a history of anthracycline use, which can cause CTRCD [6]. Contemporary radiation therapy for patients with breast cancer has been reported to have little effect on longitudinal strain or cardiac biomarkers in the short term [7, 8]. Few studies have evaluated the cardiotoxicity of trastuzumab in patients with no history of anthracycline use. Recently, the number of patients using trastuzumab without a history of anthracycline use has increased because of its reported efficacy for salivary gland cancer [9,10,11]. The age-standardized incidence rate for salivary gland cancer was 0.56 cases per 100,000 individuals worldwide and 0.99 in Japan [12, 13]. Furthermore, although previous reports of cardiotoxicity due to trastuzumab have only been reported in female patients, the use of trastuzumab among male patients is currently more common in clinical practice. To the best of our knowledge, no studies have been conducted among men without a history of anthracycline use or with salivary gland cancer who use trastuzumab.

In cardio-oncology, biomarkers such as cardiac troponin and brain natriuretic peptide (BNP), as well as echocardiographic parameters such as left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), have been used to screen for CTRCD. These markers are also recommended in the European Society of Cardiology (ESC) 2022 guidelines as clinical parameters to be examined at baseline and follow-up in patients undergoing cancer therapy [14]. In particular, GLS is an important marker for the early recognition of myocardial dysfunction. Moreover, regional LS has recently been reported in cardio-oncology as a useful marker [15, 16]. However, studies reporting sex differences in LS changes in patients treated with trastuzumab are lacking.

Thus, this study aimed to compare trends in LS and cardiac events between male and female trastuzumab-treated patients with salivary gland cancer without a history of anthracycline use.

Materials and methods

Study participants

This retrospective cohort study included trastuzumab-treated patients with salivary gland cancer with no history of anthracycline use attending International University of Health and Welfare Mita Hospital, Japan between April 2017 and March 2022. The following patients were excluded: (i) those treated with anthracycline; (ii) those without data on routine follow-up by a cardiologist; (iii) those with persistent atrial fibrillation, cardiomyopathy, or previous hospitalization due to heart failure; and (iv) those for whom measuring GLS or local LS was challenging. In our hospital, all patients treated with trastuzumab are regularly followed up by cardiologists.

Procedure for the follow-up of patients receiving trastuzumab

As shown in Fig. 1, patients who received trastuzumab were evaluated by a cardiologist before trastuzumab and after the first (first follow-up), third (second follow-up), and sixth (third follow-up) trastuzumab administrations. Follow-up after the third visit is determined by each cardio-oncologist, based primarily on echocardiographic findings. In general, patients receiving trastuzumab therapy underwent blood tests and medical, electrocardiography, echocardiography, and chest radiography examinations on the follow-up visit days. Blood tests included measurement of high-sensitivity troponin I (hsTnI), BNP, D-dimer, creatine kinase (CK), and CK-MB levels.

Fig. 1
figure 1

Follow-up and examinations in patients treated with trastuzumab. BNP, Brain natriuretic peptide; CK, Creatine kinase; ECG, Electrocardiogram; TTE, Transthoracic echocardiography

Full size image

Evaluation and definition of clinical variables

We collected basic characteristic data, including age, sex, body mass index, coexisting diseases, cardiac protective medications, cardiac biomarker levels, and echocardiographic parameters, from patients’ electronic medical records. Cancer-specific covariates, including cancer type and radiation therapy, were also recorded. Hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg or antihypertensive medication use. Diabetes mellitus was defined as glycated hemoglobin ≥ 6.5% or receipt of insulin therapy or oral medication for diabetes mellitus. Dyslipidemia was defined as a low-density lipoprotein cholesterol level > 140 mg/dl or receipt of dyslipidemia medication. Chronic kidney disease was defined as an estimated glomerular filtration rate of < 60 mL/min/1.73 m [2].

Echocardiographic assessment including regional LS

Experienced sonographers performed standard echocardiographic examinations according to the American Society of Echocardiography guidelines. Vivid E95 ultrasound systems (GE Healthcare, Chicago, Illinois, United States) were used, and the data were analyzed using GE EchoPAC software (GE Healthcare, Chicago, Illinois, United States).

LVEF was measured using the biplane Simpson’s method. Strain measurements were performed by a single sonographer using images obtained from apical long, four-chamber, and two-chamber views. GLS was measured automatically. Regional LS was measured using the same process and each mean peak strain value of five or six segments. Basal, mid, and apical LS values were calculated using values in the basal (six segments), mid (six segments), and apical (five segments) layers, respectively. Originally, LS was expressed as a negative value but was evaluated as an absolute value in this study. GLS and regional LS measurements were performed by an experienced sonographer and echocardiographic physician in a blinded manner.

Definitions of clinical outcomes

We evaluated the following clinical outcomes occurring by the third follow-up visit: (i) CTRCD (LVEF), (ii) CTRCD (GLS), (iii) heart failure requiring drug intervention, (iv) discontinuation of trastuzumab owing to cardiac events, and (v) TnI elevation. For all-cause death, data were collected until the final follow-up visit. CTRCD (LVEF) was defined as a decrease of 10% compared with the baseline value and < 53% of LVEF. CTRCD (GLS) was defined as a decrease of 15% compared with the baseline value. HsTnI level elevation was defined as > 26.8 pg/mL (99th reference percentile, standard value of the Abbot hsTnI assay). If the hsTnI level at baseline was above the reference value, elevation was defined as twice the baseline level.

Ethics approval

This study conformed to the ethical guidelines of the Declaration of Helsinki and was approved by the Ethics Committee of International University of Health and Welfare, Mita Hospital (approval number 5-21-12). The requirement for informed consent was waived due to the retrospective nature of the study.

Statistical analysis

Continuous variables with non-normal distribution and categorical variables are presented as medians (25th–75th percentiles) and numbers (percentages), respectively. The Mann–Whitney U test was used to compare continuous variables between groups. The Wilcoxon signed-rank test was used to compare continuous variables before and after trastuzumab therapy. Fisher’s exact test was used to compare the proportions of categorical variables between the groups. Kaplan–Meier curves were plotted to determine survival from CTRCD (GLS and LVEF). Time-to-event was defined as the time from diagnosis to the occurrence of CTRCD (GLS and LVEF). The Kaplan\(\:-\)Meier curves generated for CTRCD-free survival were compared using the log-rank test (male or female). Hazard ratios (HRs) for the association between clinical parameters and CTRCD were analyzed using the univariate Cox proportional hazards model. The model results are presented as adjusted HRs with 95% confidence intervals (CIs). Statistical significance was set at two-sided p values < 0.05 for all tests. Statistical analyses were performed using R software version 4.1.2 (R Foundation for Statistical Computing, Vienna, Austria).

Results

Baseline characteristics

We enrolled 71 patients who were treated with trastuzumab for salivary gland cancer at our hospital. After excluding patients who met the exclusion criteria (Figs. 2), 49 patients (mean age [range], 65 [55–71] years; males, 75.5%) were analyzed in this study. The baseline characteristics of the study participants are presented in Table 1. The male group had significantly higher rates of hypertension (54.1% vs. 16.7%, p = 0.043) and renin-angiotensin system inhibitor (RASi) use (32.4% vs. 0%, p = 0.024) than the female group. In addition, all of the present patients were HER2-positive salivary duct carcinomas.

Fig. 2
figure 2

Flow diagram of the recruitment process of patients treated with trastuzumab

Full size image
Table 1 Baseline characteristics of the study participants
Full size table

Changes in clinical parameters

The median duration by the third follow-up was 120 (111–128) days, and the median observation period by the final follow-up was 466 (293–916) days. Table 2 shows the changes in LS, LVEF, and hsTnI level by sex from baseline to the third follow-up. During the follow-up period, apical LS and GLS (p = 0.052) showed a decreasing trend in the male group, and a significant difference was found between baseline and the third follow-up apical LS results (p = 0.019).

Table 2 Changes in the longitudinal strain and troponin I after trastuzumab administration
Full size table

Clinical events in patients treated with trastuzumab

The clinical outcomes of female and male patients are shown in Table 3. No significant differences in clinical events were observed between the groups. By the third follow-up, 1 and 0 CTRCD events (LVEF) occurred in the female and male groups, respectively. CTRCD (GLS) occurred in two female and seven male patients. The median time from trastuzumab initiation to CTRCD (GLS) occurrence was 55 (23–65) days. The median time to the second follow-up was 59 (55–63) days after initiating trastuzumab treatment. Four patients with CTRCD (GLS) were diagnosed at the first and second follow-ups, respectively. Details of patients with reduced GLS are presented in Supplementary Table 1.

Table 3 Clinical events in patients who received trastuzumab therapy
Full size table

All-cause death until the final follow-up occurred in three and seven patients in the female and male groups, respectively. The Kaplan–Meier curves showed that the CTRCD-free (GLS and LVEF) survival rate in patients treated with trastuzumab at 100 days was 81.1% (95% CI: 66.8–89.7; Fig. 3A), and no significant difference was found in CTRCD (GLS and LVEF) frequency between female and male patients (log-rank test, p = 0.88; Fig. 3B). In the univariate analysis, no factors were associated with CTRCD (GLS and LVEF) in the total cohort (Supplementary Table 2). Oral administration of RASi prior to trastuzumab initiation was also not associated with CTRCD prevention.

Fig. 3
figure 3

Kaplan–Meier curves of event-free survival in patients treated with trastuzumab. Event-free survival rates in patients treated with trastuzumab are presented. Events are defined as CTRCD (LVEF and GLS) incidence. Trastuzumab was administered on day 0. CTRCD, Cancer therapy-related cardiac dysfunction; GLS, Global longitudinal strain; LS, Longitudinal strain; LVEF, Left ventricular ejection fraction

Full size image

Discussion

In this study, patients with salivary gland cancer who had received trastuzumab without prior anthracycline therapy were examined for trends in LS and frequency of CTRCD by sex; no significant differences were found in the frequency of CTRCD. A trend toward a decrease in apical LS with trastuzumab administration was observed in male patients.

In the present study, no significant difference was observed in the frequency of CTRCD between male and female patients. Females treated with anthracyclines have been reported to have a higher risk of CTRCD [17, 18]. However, a study using the claims database found no significant difference in the incidence of heart failure between males and females in patients treated with anti-HER2 monoclonal antibody therapy, although the majority of patients had breast cancer [19]. Even in patients with gastric cancer who probably did not receive anthracyclines, no difference in the occurrence of heart failure was observed between males and females. These findings are consistent with those of this study. Interestingly, patients receiving anthracyclines and patients receiving immune checkpoint inhibitors who had regional LS showed an early decrease in basal LS, [15, 16] whereas a trend toward a decrease in apical LS was observed in male patients treated with trastuzumab in the present study. A previous study reported that apical LS reduction occurs earlier than basal LS reduction, but the study cohort included patients with lymphoma who received anthracyclines [20]. The reason for this phenomenon could be that the blood supply to the myocardium is more easily impaired at the apical region than at the basal region. Two reasons could explain this phenomenon: first, wall shear stress due to coronary artery blood flow is lower in distal regions; [21, 22] thus, endothelial dysfunction is more likely to occur in the distal region, [23] and second, the apical region compared with the basal region has a higher workload and greater oxygen demand [24]. If this is the mechanism of cardiac dysfunction, male patients who are at a higher risk of coronary artery disease would also be at a higher risk of CTRCD. However, as the study results showed no sex differences, there may be other mechanisms of myocardial damage that are unique to trastuzumab. Therefore, at this time, we recommend that the same follow-up procedure be used for both male and female patients.

Left ventricular dysfunction occurs in up to 15–20% of patients at high to very high risk of CTRCD [25,26,27,28]. In the present study, all patients had no history of anthracycline use, heart failure, or cardiomyopathy and were aged < 80 years. Therefore, many of them are classified as having low-to-moderate risk according to the ESC 2022 guideline risk stratification for cardiotoxicity, and none are classified as having very high risk. Although the CTRCD (LVEF) incidence in this study was very low at 2.0%, CTRCD (GLS) incidence was as high as 18.4%. Trastuzumab-induced cardiac dysfunction should be considered common. Previous studies with long-term follow-up of trastuzumab-treated patients reported that 15% of patients had CTRCD defined by LVEF [29]. It has also been reported that decreased GLS in trastuzumab-treated patients is associated with decreased cardiopulmonary function as measured by peak oxygen consumption several years after cancer treatment [30]. On the other hand, overexpression of HER2 in salivary gland cancer is reported to be associated with higher disease activity and poorer prognosis. Therefore, discontinuation of trastuzumab should be avoided if possible [31, 32]. It has been reported that trastuzumab can be continued relatively safely with cardioprotective agents and close monitoring if LVEF remains at 40% or greater [33, 34]. Discontinuation of trastuzumab due to decreased GLS alone may be detrimental to the treatment of salivary gland cancer. Therefore, in patients with a relatively short-term decline in GLS, as in this study, management strategies such as the introduction of cardioprotective agents and long-term follow-up after the completion of trastuzumab may be considered. In the present study, none of the patients treated with trastuzumab alone had elevated TnI levels. This finding was consistent with that of previous reports of no elevation of TnI levels in patients without a history of anthracycline use [35, 36]. Our results also suggest that following up on GLS is important for the early identification of cardiac dysfunction.

The incidence of CTRCD in patients treated with trastuzumab was reported to be 3.2% without prior anthracycline therapy and 7–19% with prior anthracycline therapy, a difference of several folds [37, 38]. Until now, data of patients previously treated with anthracyclines have been more important because most of these patients had breast cancer. However, more patients without anthracycline use and more male patients are expected to be treated with trastuzumab in the future, and clinical data on patients treated with trastuzumab without previous anthracycline use are also important. Therefore, since CTRCD defined by GLS, even in patients treated with trastuzumab without anthracycline therapy, is relatively common, we believe that this important finding can be useful for daily clinical practice.

This study had several limitations. First, although this study conducted a retrospective analysis using a prospective screening program, the results may not be generalizable because this was a single-center study. Second, the sample size was small, and it is not certain whether we can truly establish the absence of sex differences based on the study findings. Third, a selection bias was considered because patients with poor echocardiographic quality were excluded. Finally, we could not examine long-term changes and outcomes. Therefore, further large-scale prospective studies with long-term results are required to strengthen the validity of our results.

Conclusions

In this study, no significant difference in the incidence of CTRCD was observed between male and female patients with salivary gland cancer treated with trastuzumab and who had not previously received anthracycline. In trastuzumab-treated patients without a history of anthracycline administration, attention should be paid to the occurrence of CTRCD, irrespective of gender.

Availability of date and materials

The data that support the findings of our study are available on request from the corresponding author.

Abbreviations

BNP:

Brain natriuretic peptide

CTRCD:

Cancer treatment-related cardiac dysfunction

ESC:

European Society of Cardiology

GLS:

Global longitudinal strain

HER2:

Human epidermal growth factor receptor 2

LS:

Longitudinal strain

LVEF:

Left ventricular ejection fraction

References

  1. Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365:1273–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, et al. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 2013;382:1021–8.

    Article  CAS  PubMed  Google Scholar 

  3. Romond EH, Jeong JH, Rastogi P, et al. Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2012;30:3792–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tarantini L, Cioffi G, Gori S, et al. Trastuzumab adjuvant chemotherapy and cardiotoxicity in real-world women with breast cancer. J Card Fail. 2012;18:113–9.

    Article  CAS  PubMed  Google Scholar 

  5. Van Cutsem E, Sagaert X, Topal B, Haustermans K, Prenen H. Gastric cancer. Lancet. 2016;388:2654–64.

    Article  PubMed  Google Scholar 

  6. Cardinale D, Colombo A, Bacchiani G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015;131:1981–8.

    Article  CAS  PubMed  Google Scholar 

  7. Yu AF, Ho AY, Braunstein LZ, Thor ME, et al. Assessment of Early Radiation-Induced changes in left ventricular function by myocardial strain imaging after breast Radiation Therapy. J Am Soc Echocardiogr. 2019;32(4):521–8.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Chufal K, Ahmad I, Prakash A et al. Cardiac markers in left-sided breast cancer patients receiving adjuvant radiotherapy: a prospective study. Cardiooncology. 2024; 8;10(1):21.

  9. Hanna GJ, Bae JE, Lorch JH, et al. The benefits of adjuvant trastuzumab for HER-2-positive salivary gland cancers. Oncologist. 2020;25:598–608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kawakita D, Nagao T, Takahashi H, et al. Survival benefit of HER2-targeted or androgen deprivation therapy in salivary duct carcinoma. Ther Adv Med Oncol. 2022;14:17588359221119538.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Takahashi H, Tada Y, Saotome T, et al. Phase II trial of Trastuzumab and Docetaxel in patients with human epidermal growth factor receptor 2-Positive Salivary Duct Carcinoma. J Clin Oncol. 2019;37:125–34.

    Article  CAS  PubMed  Google Scholar 

  12. Ferlay J, Ervik M, Lam F et al. (2024). Global Cancer Observatory: Cancer Today (version 1.1). Lyon, France: International Agency for Research on Cancer. https://gco.iarc.who.int/today, accessed 12 April 2024.

  13. Tomohiro Matsuda H, Sugiyama. April, Manami Konda and Kumiko Saika. Rare Cancer Data Book Based on the Population-based Cancer Registries in Japan. http://ncc.utj.co.jp/, Accessed 12th 2024.

  14. Lyon AR, López-Fernández T, Couch LS, et al. 2022 ESC guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43:4229–361.

    Article  PubMed  Google Scholar 

  15. Tamura Y, Tamura Y, Takemura R, et al. Longitudinal strain and troponin I elevation in patients undergoing immune checkpoint inhibitor therapy. JACC CardioOncol. 2022;4:673–85.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Saijo Y, Kusunose K, Okushi Y, Yamada H, Toba H, Sata M. Relationship between regional left ventricular dysfunction and cancer-therapy-related cardiac dysfunction. Heart. 2020;106:1752–8.

    Article  CAS  PubMed  Google Scholar 

  17. Lipshultz SE, Lipsitz SR, Mone SM, et al. Female sex and higher drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. N Engl J Med. 1995;332:1738–43.

    Article  CAS  PubMed  Google Scholar 

  18. Herrmann J, Lerman A, Sandhu NP, Villarraga HR, Mulvagh SL, Kohli M. Evaluation and management of patients with heart disease and cancer: cardio-oncology. Mayo Clin Proc. 2014; 89: 1287–1306.

  19. Suzuki Y, Kaneko H, Tamura Y, et al. Sex-specific differences in the risk of heart failure following anti-HER2 monoclonal antibody therapy. Oncology. 2023;101:358–61.

    Article  CAS  PubMed  Google Scholar 

  20. Xu Y, Shi J, Zhao R, et al. Anthracycline induced inconsistent left ventricular segmental systolic function variation in patients with lymphoma detected by three-dimensional speckle tracking imaging. Int J Cardiovasc Imaging. 2019;35:771–9.

    Article  PubMed  Google Scholar 

  21. Salvucci FP, Perazzo CA, Gurfinkel E, et al. A patient-specific method for the evaluation of wall shear stress in human coronary arteries. Annu Int Conf IEEE Eng Med Biol Soc. 2010;2010:3788–91.

    CAS  PubMed  Google Scholar 

  22. Pinto SI, Campos JB. Numerical study of wall shear stress-based descriptors in the human left coronary artery. Comput Methods Biomech Biomed Engin. 2016;19(13):1443–55.

    Article  CAS  PubMed  Google Scholar 

  23. Siasos G, Sara JD, Zaromytidou M, et al. Local low shear stress and endothelial dysfunction in patients with nonobstructive coronary atherosclerosis. J Am Coll Cardiol. 2018;71(19):2092–102.

    Article  PubMed  Google Scholar 

  24. Sengupta PP, Khandheria BK, Korinek J, et al. Apex-to-base dispersion in regional timing of left ventricular shortening and lengthening. J Am Coll Cardiol. 2006;47(1):163–72.

    Article  PubMed  Google Scholar 

  25. Martel S, Maurer C, Lambertini M, Pondé N, De Azambuja E. Breast cancer treatment-induced cardiotoxicity. Expert Opin Drug Saf. 2017;16:1021–38.

    Article  CAS  PubMed  Google Scholar 

  26. de Azambuja E, Ponde N, Procter M, et al. A pooled analysis of the cardiac events in the trastuzumab adjuvant trials. Breast Cancer Res Treat. 2020;179:161–71.

    Article  PubMed  Google Scholar 

  27. Eiger D, Pondé NF, Agbor-Tarh D, et al. Long-term cardiac outcomes of patients with HER2-positive breast cancer treated in the adjuvant lapatinib and/or trastuzumab treatment optimization trial. Br J Cancer. 2020;122:1453–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Tan-Chiu E, Yothers G, Romond E, et al. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2–overexpressing breast cancer: NSABP B-31. J Clin Oncol. 2005;23:7811–9.

    Article  CAS  PubMed  Google Scholar 

  29. Upshaw JN, Finkelman B, Hubbard RA, et al. Comprehensive assessment of changes in left ventricular diastolic function with contemporary breast cancer therapy. JACC Cardiovasc Imaging. 2020;13:198–210.

    Article  PubMed  Google Scholar 

  30. Yu AF, Flynn JR, Moskowitz CS, et al. Long-term cardiopulmonary consequences of treatment-induced cardiotoxicity in survivors of ERBB2-positive breast cancer. JAMA Cardiol. 2020;5:309–17.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Filippini DM, Pagani R, Tober N, et al. HER2-targeted therapies for salivary gland cancers. Oral Oncol. 2024;148:106612.

    Article  CAS  PubMed  Google Scholar 

  32. Etges A, Pinto DS Jr, Kowalski LP, et al. Salivary duct carcinoma: immunohistochemical profile of an aggressive salivary gland tumour. J Clin Pathol. 2003;56(12):914–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lynce F, Barac A, Geng X, et al. Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study. Breast Cancer Res Treat. 2019;175(3):595–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Leong DP, Cosman T, Alhussein MM, et al. Safety of Continuing Trastuzumab despite mild cardiotoxicity: a phase I Trial. JACC CardioOncol. 2019;1(1):1–10.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Díaz-Antón B, Madurga R, Zorita B, et al. Early detection of anthracycline- and trastuzumab-induced cardiotoxicity: value and optimal timing of serum biomarkers and echocardiographic parameters. ESC Heart Fail. 2022;9:1127–37.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Zardavas D, Suter TM, Van Veldhuisen DJ, et al. Role of troponins I and T and N-terminal prohormone of brain natriuretic peptide in monitoring cardiac safety of patients with early-stage human epidermal growth factor receptor 2-positive breast cancer receiving trastuzumab: a herceptin adjuvant study cardiac marker substudy. J Clin Oncol. 2017;35:878–84.

    Article  CAS  PubMed  Google Scholar 

  37. Guglin M, Krischer J, Tamura R, et al. Randomized trial of lisinopril versus carvedilol to prevent trastuzumab cardiotoxicity in patients with breast cancer. J Am Coll Cardiol. 2019;73:2859–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Dang C, Guo H, Najita J, et al. Cardiac outcomes of patients receiving adjuvant weekly paclitaxel and trastuzumab for node-negative, ERBB2-positive breast cancer. JAMA Oncol. 2016;2:29–36.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to express our gratitude to all the participants and staff involved in this study, especially Rika Takeyasu and Yui Shiga, for data management.

Funding

Not applicable.

Author information

Authors and Affiliations

  1. Cardiovascular Center, International University of Health and Welfare Mita Hospital, Tokyo, Japan

    Yudai Tamura

  2. Pulmonary Hypertension Center, International University of Health and Welfare Mita Hospital, 1-4-3 Mita, Minato-ku, Tokyo, 108-8329, Japan

    Yuichi Tamura

  3. Department of Head and Neck Oncology and Surgery, International University of Health and Welfare Mita Hospital, Tokyo, Japan

    Yuichiro Tada

Authors
  1. Yudai Tamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuichi Tamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuichiro Tada
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Yudai T contributed to the study conception, design, analysis and interpretation of data. Yudai T contributed drafting of the manuscript. Yuichi T contributed analysis and interpretation of data and revising it critically for important intellectual content. Yuichiro Tada contributed revising it critically for important intellectual content. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Yuichi Tamura.

Ethics declarations

Ethics approval and consent to participate

This study conformed to the ethical guidelines of the Declaration of Helsinki, and was approved by the Ethics Committee of the International University of Health and Welfare, Mita Hospital (approval number 5-21-12). The requirement for informed consent was waived due to the retrospective nature of the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tamura, Y., Tamura, Y. & Tada, Y. Frequency of and sex differences in cancer treatment-related cardiac dysfunction in trastuzumab-treated patients with salivary gland cancer: a retrospective cohort study. Cardio-Oncology 10, 44 (2024). https://doi.org/10.1186/s40959-024-00248-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s40959-024-00248-8

Keywords

Cardio-Oncology

ISSN: 2057-3804

Contact us