Function In Breast Cancer Patients Research Articles

Assessment of right ventricular dysfunction in breast cancer patients undergoing anthracycline and trastuzumab treatment

Abstract Background Anthracyclines and trastuzumab continue to be within the most popular systemic agents used in breast cancer treatment. Nonetheless, their cardiotoxic effects contribute to significant morbidity and mortality, which have been extensively studied and acknowledged. Left ventricular impairment and remodeling due to chemo- and target-therapy induced cardiotoxicity has been well described. However, effects on right ventricular function have not been fully elucidated and are incompletely understood. Purpose We aim to comprehensively assess right ventricular function in breast cancer patients before and during treatment with anthracyclines and trastuzumab. Methods We prospectively evaluated echocardiographic right ventricle (RV) parameters in 160 women (median age 48, IQR 43.00 - 57.00) diagnosed with breast cancer undergoing treatment with doxorubicin, trastuzumab or its combination. These patients were referred to a national cardiac reference centre to assess cancer therapy related cardiovascular dysfunction (CTRCD) risk. Two-dimensional echocardiography with speckle tracking imaging of left ventricle (LV) and RV was performed at baseline, 3 and 6 months. Right ventricular function was assessed with tricuspid annular plane systolic excursion (TAPSE), S’wave of the tricuspid annulus (S'), fractional area change (FAC), and free wall strain (RV-FWS). We designed a composite variable of right ventricular dysfunction constituted by any decrease in systolic function as evidenced by standard cutoff values of TAPSE, FAC, S’wave and RV-FWS. Descriptive statistics were calculated. Categorical values were compared using either the Fisher’s exact test or Chi-squared test and differences between means were assessed with the Kruskal-Wallis test or the Wilcoxon test as appropriate. Results TAPSE and S’ were significantly reduced from baseline, at 3 and 6 months, respectively (TAPSE: 21.62 ± 2.22, 21.00 ± 1.83, 20.72 ± 1.99, P=<0.001; S’:12.16 ± 1.91, 11.70 ± 1.76, 11.51 ± 1.53, P = 0.012) (Table 1). There were no significant changes in right ventricular echocardiographic parameters comparing patients with and without CTRCD, nevertheless, a notable proportion in both groups was observed (see Table 2). Conclusions There is a progressive decline in right ventricular systolic function over treatment with anthracyclines and trastuzumab. Even though RV dysfunction does not significantly differ between patients with or without cardiotoxicity, the high proportion observed highlights the need for comprehensive echocardiographic assessments.

Early Postoperative Exercise To Promote Recovery Of Shoulder Function In Breast Cancer Patients: Randomized Controlled Trial

Early Postoperative Exercise To Promote Recovery Of Shoulder Function In Breast Cancer Patients: Randomized Controlled Trial

Effect of physical exercise on postoperative shoulder mobility and upper limb function in patients with breast cancer: a systematic review and meta-analysis.

The shoulder pain and reduced range of motion caused by breast cancer seriously affect the quality of life of women. Such persistent impairments can escalate into chronic pain, diminished muscle strength, lymphedema, and compromised cardiorespiratory health potentially culminating in permanent disability. This systematic review aims to evaluate how physical exercise impacts shoulder mobility and upper limb function in breast cancer patients post-surgery, examining various aspects of exercise such as type, intensity, duration, frequency, and intervention timing to determine the influence on outcomes. A comprehensive search was conducted across seven databases up to April 16, 2024. Two reviewers independently assessed randomized controlled trials (RCTs) focusing on the effects of physical exercise on postoperative outcomes in breast cancer patients. Quality was assessed using the Cochrane risk of bias tool, with meta-analyses and publication bias tests performed via RevMan5.4, and evidence quality evaluated using GRADEPro. Effect sizes were calculated using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Twenty studies (25 RCTs involving 2,171 patients) were included for both the systematic review and the meta-analysis. Meta-analysis confirmed that physical exercise significantly enhanced shoulder flexion (SMD =0.59; 95% CI: 0.32, 0.86; P<0.001) and abduction (SMD =1.01; 95% CI: 0.43, 1.60; P<0.001) in postoperative patients, and improved upper limb function (SMD =0.87; 95% CI: 0.48, 1.26; P<0.001). Subgroup analyses indicated that comprehensive exercise, particularly when performed ≤3 times a week or over 8-12 weeks, was most effective for improving shoulder flexion, while shorter durations (<8 weeks) and similar frequencies were optimal for abduction. Resistance exercises, especially when started early (<2 weeks post-surgery), showed significant benefits for upper limb function. The included studies were of moderate to high quality, though some lacked detailed reporting on blinding or allocation concealment. Analysis suggests that the timing of intervention initiation, along with exercise type and frequency, may contribute to observed variations in outcomes. Evidence quality assessments did not reveal significant issues with indirectness or imprecision, and no significant publication bias was detected. Given the low heterogeneity and absence of significant downgrade factors, intermediate evidence quality was assigned for upper limb function and shoulder abduction, with high quality for shoulder flexion. Physical exercise is notably effective in enhancing both upper limb function and shoulder mobility in breast cancer patients, with the timing and frequency of exercise interventions influencing these improvements. This provides valuable evidence for clinical rehabilitation strategies.

Impact of neoadjuvant chemotherapy on perioperative immune function in breast cancer patients: a propensity score-matched retrospective study

To evaluate the impact of neoadjuvant chemotherapy on perioperative immune function in breast cancer patients, focusing on CD3+, CD4+, CD8+, and natural killer (NK) cells, as well as the CD4+/CD8+ ratio. We retrospectively reviewed medical records of breast cancer patients who underwent surgery with or without neoadjuvant chemotherapy at our medical center from January 2020 to December 2022. Patients were matched 1:1 based on propensity scores. Immune cell proportions and the CD4+/CD8+ ratio were compared on preoperative day one and postoperative days one and seven. Among matched patients, immune cell proportions and the CD4+/CD8+ ratio did not significantly differ between those who received neoadjuvant chemotherapy and those who did not at any of the three time points. Similar results were observed in chemotherapy-sensitive patients compared to the entire group of patients who did not receive neoadjuvant chemotherapy. However, chemotherapy-insensitive patients had significantly lower proportions of CD4+ and NK cells, as well as a lower CD4+/CD8+ ratio, at all three time points compared to patients who did not receive neoadjuvant chemotherapy. Neoadjuvant chemotherapy may impair immune function in chemotherapy-insensitive patients, but not in those who are sensitive to the treatment.

Dynamic changes in brain glymphatic function during preoperative chemotherapy in breast cancer patients.

The current study aimed to investigate the dynamic changes in brain glymphatic function during chemotherapy in breast cancer patients (BCP) and their correlation with cognitive function. A total of 40 healthy female participants (control group) and 80 female BCP were included. Various cognitive assessment tools were used to evaluate cognitive function. Diffusion tensor imaging along the perivascular space was employed to measure brain glymphatic function. Following chemotherapy, BCP exhibited a significant decline in various cognitive scores. After chemotherapy, the along the perivascular space index, a parameter indicating brain glymphatic function, was slightly higher than that at baseline and the control group levels and was correlated with cognitive scores. This study unveiled a close relationship between the dynamic changes in brain glymphatic function after chemotherapy and cognitive function in BCP. Our findings contribute to a deeper understanding of the brain mechanisms underlying chemotherapy-related cognitive impairment and provide a theoretical basis for future interventions and treatments. In addition, they offer a new perspective for exploring the relationship between brain function and cognitive states.

Toward better understanding and management of chemobrain: the potential utilities of the MemTrax memory test

ObjectiveTo study the effects of chemotherapy on cognitive function in breast cancer patients, and to investigate the relationship of MemTrax test of memory and related functions to the FACT-Cog functional self-assessment for the evaluation and management of chemobrain.MethodsIn this prospective cohort study, clinical information of pathologically confirmed female breast cancer patients who decided to receive chemotherapy were collected in a questionnaire which was developed for this study and provided as a supplementary file. The FACT-Cog self-assessment and MemTrax test were administered before and after the chemotherapy treatments. Patients with chemobrain were identified using published criteria based on FACT-Cog scores, and MemTrax scores from chemobrain patients were analyzed.ResultsFifty-six patients participated in this study, of which 41 participants completed 4 or more cycles of chemotherapy and were included in the final analyses here. Using the reported high end of minimal clinical differences (10.6 points) of FACT-Cog before and after chemotherapy, 18 patients suffered from chemobrain in this study. In these 18 chemobrain patients, no cognitive impairments were detected by MemTrax, which paradoxically demonstrated an improvement in the normal cognitive range.ConclusionThe cognitive impairment induced by chemotherapy in breast cancer patients is detectable by the FACT-Cog in a Chinese cohort but is not detected by the MemTrax memory test. The fact that the more objective MemTrax could not detect the impairment could alleviate patients’ concerns which in turn would be beneficial for patients’ mental health.

Immune checkpoint inhibitors-related endocrinopathies exhibit increased severity in breast cancer patients: a real-world study.

This study aims to systematically evaluate the incidence of immune checkpoint inhibitors (ICIs)-related endocrinopathies and their onset time in patients with breast cancer (BC) in a real-world setting. An analysis was conducted on the medical records of 122 BC patients who underwent ICIs therapy at the Department of Breast Surgery, Guangdong Provincial People's Hospital, from April 2019 to September 2021. Follow-up data continued until October 2022. The research indicated that 60.66% of BC patients experienced ICI-related endocrinopathies. The endocrinopathies included pituitary injury (7.38%), primary thyroid dysfunction (34.43%), supranormal fasting blood glucose or glycohemoglobin levels (16.39%), and adrenal injury (2.46%). Subgroup analyses were further performed based on clinical characteristics, demonstrated variability in the incidence of ICI-related endocrinopathies. Notably, subpopulations harboring genetic mutations exhibited a markedly higher prevalence of hypophysitis, as evidenced by a statistically significant association (P = 0.022). Similarly, individuals with HER2 positivity were found to have a significantly increased incidence of pancreatic islet injury (P = 0.023). Moreover, the study documented that the median onset times of ICIs-related endocrinopathies in pituitary, thyroid, pancreatic, and adrenal damage were 264, 184, 99 and 141 days, respectively, which were substantially longer compared to previous reports involving other tumors. Remarkably, even after 500 days of initiating ICI therapy, new cases of ICI-related endocrine disorders continue to emerge, suggesting a situation of delayed onset of ICI-related endocrinopathies in BC patients. The retrospective analysis confirmed a higher incidence and longer median onset time of ICI-related endocrinopathies in BC patients compared to other cancers. These outcomes underscore the critical need for regular and extended monitoring of endocrine functions in BC patients receiving ICI therapy, advocating for personalized monitoring approaches based on individual clinical profiles.

(118) ORGASM AND HEART RATE VARIABILITY IN FEMALE BREAST CANCER SURVIVORS: RESULTS FROM A PSYCHOPHYSIOLOGY STUDY

Abstract Introduction Over 70 % of female breast cancer survivors suffer from sexual dysfunction. Sexual dysfunction can cause great amounts of stress and negatively impact overall health and well-being. Most studies focus on sexual arousal disorders and hypoactive sexual desire disorders. The research on orgasm in this specific group is limited. A better understanding of sexual function in breast cancer patients may yield potential targets for new treatment strategies for sexual dysfunction in this population. Low heart rate variability (HRV) has been shown to be predictive of erectile dysfunction and female sexual arousal as well as orgasm frequency. Reduced HRV and low cardiac vagal tone have previously been reported in breast cancer survivors during the first year post-treatment. If HRV is a reliable indicator of female sexual dysfunction, it could be used to assess and monitor it in a clinical setting. Objectives This study aimed to explore whether there is a link between HRV and both, sexual arousal and the ability to orgasm. We were expecting to find a difference in HRV between breast cancer survivors and healthy controls as well as orgasmic and anorgasmic women. Methods Participants were prescreened during a telephone interview. We included 40 premenopausal breast cancer survivors currently on hormonal treatment with an age range of 29 to 57 years (M = 43.5, SD = 6.4) and 20 healthy controls with an age range of 22 to 35 (M = 27.6, SD = 3.2). The vaginal pulse amplitude, heart rate variability (SDNN), subjective sexual arousal and self-reported number of orgasms were assessed in response to audiovisual sexual stimuli and vibrotactile clitoral stimulation in breast cancer survivors and healthy controls. Validated patient-reported outcome measures were used to assess sexual dysfunctions (Female Sexual Function Index, Female Sexual Distress Scale − Desire/Arousal/Orgasm), sexual self-esteem (Sexual Self-Esteem Inventory-Short Form), health-related quality of life (Patient-Reported Outcomes Measurement Information System 29 (PROMIS-29) profile questionnaire). Results Breast cancer survivors showed lower sexual function, health-related quality of life, sexual self-esteem and higher sexual distress than healthy controls. Preliminary results show a difference in baseline HRV scores between healthy controls and breast cancer survivors. However, this finding is likely due to age differences between our two groups and not cancer treatment effects. We could find no apparent differences in baseline HRV between anorgasmic and orgasmic women. Further analyses on the predictive value of HRV during sexual arousal for orgasm occurrence will be conducted. Conclusions Our data did not corroborate either of our hypotheses related to baseline HRV. For the evaluation of HRV as a predictor for orgasm occurrence, further exploratory analyses will follow. More research on the physiological parameters of sexual dysfunction is needed to reveal underlying mechanisms and find targets for future therapies.

Factors associated with perceived cognitive function in breast cancer patients treated with chemotherapy: A multicenter cross-sectional study

PurposeThis study aimed to investigate the factors associated with perceived cognitive function among breast cancer patients treated with chemotherapy in China. MethodsThe study was a multicenter cross-sectional design. Data were collected from 10 public hospitals in China between April 2022 and February 2023. A total of 741 participants completed questionnaires assessing sociodemographic and medical characteristics, perceived cognitive function, sleep quality, fatigue, anxiety, and depression. Hierarchical multiple regression analysis was used to assess the determinants of cognitive function. ResultsThe hierarchical multiple regression model accounted for 31.5% of variation in perceived cognitive function (sociodemographic 4.5%; medical 6.6%; exercise frequency 6.6%; sleep quality 2.1%; fatigue 2.8%; anxiety combined with depression 9.0%). Education level, chemotherapy type, number of chemotherapy cycles, and cyclophosphamide drug use were significant predisposing factors of perceived cognitive function (p < 0.001). Exercising ≥3 times/week (p < 0.001) was a significant factor positively influencing perceived cognitive function, meanwhile, anxiety (p < 0.001) and depression (p < 0 0.001) were negative factors. ConclusionOur findings suggest that patients with low education levels, postoperative chemotherapy, cyclophosphamide treatment, and a greater number of chemotherapy cycles need more assessment. Sedentary patients, those who have never exercised, and those with anxiety or depression all showed greater cognitive decline. By identifying susceptible populations, encouraging regular exercise, and addressing anxiety and depression, healthcare professionals can contribute significantly to prevent patients’ cognitive decline throughout chemotherapy.

Comprehensive Assessment of Cardiac Function in Breast Cancer Patients: Integrating Multiparametric Speckle Tracking Imaging and Conventional Echocardiography Parameters.

Purpose The purpose of this study is to comprehensively evaluate the role of different echocardiography parameters in breast cancer patients undergoing chemotherapy. While echocardiography examination with calculation of ejection fraction (EF), is pivotal for patient monitoring, its operator dependence and insensitivity to subtle changes in left ventricular (LV) contractility present challenges. Global longitudinal strain (GLS), derived from speckle tracking, is more sensitive and stable than EF. Our research aimed to delineate supplementary echocardiography measurements beneficial for the cardiological monitoring of breast cancer patients. Methods Patients were followed up with echocardiography at baseline, during, and after the chemotherapy. Conventional echocardiography and multiple speckle tracking imaging parameters including myocardial work index, atrial strain, twist, and automatic EF were investigated. Results A total of 25 patients were recruited. A subset (15/25) exhibited pronounced GLS reduction, associated with decreased EF and altered cardiac mechanics. Patients with unchanged GLS were often hypertensive and on specific medications, in particular angiotensin-converting enzyme inhibitors (ACE inhibitors)/angiotensin II receptor blockers (ARBs), potentially indicating protective effects. Despite stability in other parameters, GLS and EF sensitivity highlight their importance. A strong correlation between manual and automated EF measurement methods was also observed. Conclusion Despite the small sample size, across diverse echocardiography parameters, GLS and EF are primarily affected by chemotherapy. Hypertensive individuals exhibited lower susceptibility to chemotherapy-induced damage, likely attributed to the cardioprotective properties of ACE inhibitors and angiotensin II receptor blockers. A strong correlation between automatic and Simpson-based EF was found.

Short-term effects of a new resistance exercise approach on physical function during chemotherapy after radical breast cancer surgery: a randomized controlled trial

BackgroundApproximately 30% of post-operative breast cancer patients develop shoulder joint movement disorders affecting routine upper limb movement. This study discusses the impact of a neuromuscular joint facilitation (NJF) method on the physical function of breast cancer patients experiencing shoulder dysfunction during chemotherapy after radical surgery.MethodsThis study included 162 female patients who have unilateral breast cancer in a cancer hospital in China. They developed shoulder joint mobility disorders during chemotherapy within 1–3 months postoperatively. These patients were divided into three groups: NJF, conventional rehabilitation (conventional group), and control groups. The clinical examination included the maximum passive and active range of motion (ROM) of the shoulder (flexion, extension, abduction, adduction, and external and internal rotation). Other evaluations included a pain score using a visual analog scale (VAS), grip strength, and supraspinatus muscle thickness. All tests were evaluated pre-and post-intervention.ResultsThe NJF group showed a significant increase in all shoulder ROM angles post-intervention. In the conventional group, all other ROM values increased significantly, except passive external rotation ROM. In the control group, all other ROM values increased significantly, except passive and active external rotation ROM. All three groups had decreased VAS scores, increased grip strength, and supraspinatus muscle thickness post-intervention during active abduction. In the control group, the supraspinatus contraction rate decreased significantly at 60° and 90° abduction post-intervention compared to that at pre-intervention.ConclusionThis study revealed that NJF during chemotherapy had positive clinical intervention effects, improving shoulder joint mobility disorders, pain, grip strength, and external rotation following radical breast cancer surgery.Clinical trial registrationChinese Clinical Trial Registry; https://www.chictr.org.cn/ (ChiCTR2300073170), registered (03/07/2023).

Effect of Taichi on cognitive function in Breast cancer patients undergoing radiotherapy: A randomized controlled trial

ObjectiveTo evaluate the short-term effect of Tai Chi on cognitive function in breast cancer patients undergoing radiotherapy compared to the control group receiving moderate intensity walking. DesignParallel, single blinded, randomized controlled trial. SettingMangaluru, Karnataka, India. Participants44 female post-surgery Breast cancer patients undergoing radiotherapy. InterventionsBased on the inclusion criteria patients were randomly assigned into two groups of 22 each. Group A received the Taichi intervention and Group B received the moderate-intensity walking for 30 min,5 times per week for 3 weeks. Outcome measureFunctional Assessment of Cancer Therapy Cognitive scale version 3 (FACT-Cog 3) RandomisationEach random number was concealed separately within a small opaque envelope (SNOSE) and the subjects were equally allocated into two groups with an allocation of 1:1. Statistical analysisIndependent sample t-test for between the group comparison and paired t-test for within the group comparison. ResultsThere were no statistically significant results found between the groups (p-value > 0.05). ConclusionThe present randomized controlled trial showed that Tai Chi did not improve the cancer-related cognitive Impairment in Breast cancer patients compared to moderate intensity walking. Clinical Trial Registration number: CTRI/2021/08/036012.

Longitudinal assessment of chemotherapy-induced brain connectivity changes in cerebral white matter and its correlation with cognitive functioning using the GQI.

Breast cancer was the most prevalent type of cancer and had the highest incidence rate among women worldwide. The wide use of adjuvant chemotherapy might have a detrimental effect on the human brain and result in chemotherapy-related cognitive impairment (CICI) among breast cancer patients. Furthermore, prior to chemotherapy, patients reported cancer-related cognitive impairment (CRCI), which might be due to physiological factors or mood symptoms. The present longitudinal study aimed to investigate microstructural and macroscale white matter alterations by generalized q-sampling imaging (GQI). The participants were categorized into a pre-chemotherapy group (BB) if they were diagnosed with primary breast cancer and an age-matched noncancer control group (HC). Some participants returned for follow-up assessment. In the present follow up study, 28 matched pairs of BB/BBF (follow up after chemotherapy) individuals and 28 matched pairs of HC/HCF (follow up) individuals were included. We then used GQI and graph theoretical analysis (GTA) to detect microstructural alterations in the whole brain. In addition, we evaluated the relationship between longitudinal changes in GQI indices and neuropsychological tests as well as psychiatric comorbidity. The results showed that disruption of white matter integrity occurred in the default mode network (DMN) of patients after chemotherapy, such as in the corpus callosum (CC) and middle frontal gyrus (MFG). Furthermore, weaker connections between brain regions and lower segregation ability were observed in the post-chemotherapy group. Significant correlations were observed between neuropsychological tests and white matter tracts of the CC, MFG, posterior limb of the internal capsule (PLIC) and superior longitudinal fasciculus (SLF). The results provided evidence of white matter alterations in breast cancer patients, and they may serve as potential imaging markers of cognitive changes. In the future, the study may be beneficial to create and evaluate strategies designed to maintain or improve cognitive function in breast cancer patients undergoing chemotherapy.

Comparison of effects of tamoxifen and Toremifene on hepatic function and serum lipids in breast cancer patients during adjuvant endocrine therapy.

To investigate the effects of tamoxifen (TAM) and toremifene (TOR) on hepatic function and serum lipid levels in breast cancer patients receiving adjuvant endocrine therapy. The clinical data of 597 early breast cancer patients treated at the First Affiliated Hospital of Nanjing Medical University between January 2016 and December 2022 were collected. All the patients received standard adjuvant endocrine therapy with TAM or TOR after chemotherapy. Hepatic function and serum lipid data of all patients before and at 6 months and 1, 2, and 3 years after the treatment were collected retrospectively and analyzed statistically. There: no negative effect on hepatic function was observed in patients treated with either TAM or TOR. The triglyceride levels in both groups increased during treatment, and the effect of TAM on improving total cholesterol levels was stronger. Total cholesterol levels were not affected by time or treatment regimen. The low-density lipoprotein cholesterol levels decreased in both groups, and the effect was similar between groups. TAM can decrease the high-density lipoprotein cholesterol levels, whereas TOR can increase the high-density lipoprotein cholesterol levels, and there was a significant difference between groups. In the postoperative adjuvant endocrine therapy, TOR and TAM will not negatively impact the hepatic function of breast cancer patients, and TOR is better than TAM in the management of serum lipids; therefore, it may be a better choice for clinical medication.

Biological and psychological predictors of cognitive function in breast cancer patients before surgery.

Research suggests that cancer-related cognitive impairment (CRCI) can occur before breast cancer (BC) treatment. The limited extant evidence suggests the underlying mechanisms could be stress-related. Potential psychological and biological predictors of CRCI prior to any BC treatment were examined. 112 treatment-naïve women with BC and 67 healthy controls (HC) completed a neuropsychological test battery to assess cognitive impairment and a self-report battery to assess cognitive complaints, cancer-related stress, depressive and anxiety symptoms. Morning and evening cortisol and α-amylase were collected from saliva. Multilinear regressions were conducted. Treatment-naïve BC patients were more frequently impaired in verbal memory and processing speed and reported more cognitive complaints (all p < .001) than HC. BC patients and HC did not differ in overall cognitive impairment (p = .21). Steeper α-amylase, lower cancer-related stress and younger age was associated with better overall cognitive function in treatment-naïve BC patients. Higher depressive symptoms predicted higher levels of cognitive complaints in BC patients. Overall, these findings suggest that stress plays a role in CRCI. This study is the first to associate α-amylase with cognitive function in cancer patients, informing future research. The findings on impairment in processing speed and verbal memory among treatment-naïve BC highlight the need to screen for such impairments among BC patients and indicate that future studies on CRCI should include baseline assessments prior to BC treatment. If replicated, these findings could inform the development and testing of appropriate interventions to decrease CRCI among cancer patients. NCT04418856, date of registration: 06.05.2020.

The effects of trastuzumab therapy on endothelial functions of breast cancer patients.

Breast cancer is among the highest causes of morbidity and mortality in women. Trastuzumab therapy, which is known to be significantly cardiotoxic, is mainly used to treat patients with resistant breast cancer, including estrogen receptor-positive type. We aimed to show the effects of trastuzumab therapy on endothelial functions of breast cancer patients. In this study, a total of 26 participants (24 female and 2 male patients, minimum age: 38 years, maximum age: 79 years, and mean age 57.3±12.7 years) were enrolled in the study. For the statistical evaluation of data, we classified the participants of the study as follows: Pretreatment: Before trastuzumab therapy; Treatment Period 1: 1 month after the first dose of trastuzumab; Treatment Period 2: 4 months after the first dose of trastuzumab; Treatment Period 3: 12 months after the first dose of trastuzumab. We conducted repeated-measures analysis of variance (Greenhouse-Geisser) and paired-sample t-tests to statistically compare the groups using flow-mediated dilation measurements. We determined that there are statistically significant differences between flow-mediated hyperemia and ratio values (flow-mediated dilation) of the groups (p<0.009 and p<0.001, respectively). Our data indicate that trastuzumab therapy could have negative effects on endothelial functions in breast cancer patients.

Intrinsic Wave Velocity Propagation: A Novel Parameter for Assessing the Effect of Anthracycline Chemotherapy Agents on Cardiac Diastolic Function in Breast Cancer Patients.

Anthracycline chemotherapeutic agents have significant cardiotoxicity. The present study emphasized the effect of anthracycline chemotherapy drugs on left ventricular (LV) myocardial stiffness in breast cancer patients by measuring the intrinsic wave velocity propagation (IVP), and evaluating the potential clinical value of IVP in detecting early LV diastolic function impairment. A total of 68 newly diagnosed breast cancer patients, who were treated with anthracycline-based chemotherapy, were analyzed. Transthoracic echocardiography was performed at baseline (T0), and after 1, 2, 3, 4 and 8 chemotherapeutic cycles (T1, T2, T3, T4 and T5, respectively). Then, the IVP, LV strain parameters [global longitudinal strain (GLS), longitudinal peak strain rate at systole (LSRs), longitudinal peak strain rate at early diastole (LSRe), longitudinal peak strain rate at late diastole (LSRa), and the E/LSRe ratio], and conventional echocardiographic parameters were obtained and further analyzed. A relative reduction of >15% in GLS was considered a marker of early LV subclinical dysfunction. Compared to the T0 stage, IVP significantly increased at the T1 stage. However, there were no significant changes in GLS, LSRs, or LSRe between the T0 and T1 stages. These parameters significantly decreased from the T2 stage. LSRa started to significantly decrease at the T5 stage, and the E/LSRe ratio started to significantly increase at the T3 stage (all P<0.05). At the T0 stage, IVP (AUC=0.752, P<0.001) had a good predictive value for LV subclinical dysfunction after chemotherapy. IVP is a potentially sensitive parameter for the early clinical assessment of anthracycline-related cardiac diastolic impairment.

Investigation of the relationship between spinal posture and mobility to respiratory muscle strength and pulmonary functions in unilateral breast cancer surgery survivors: a cross-sectional study.

Despite the research on structural and functional changes that may occur in breast cancer survivors, no study has investigated the relationship between spinal characteristics and the respiratory system. Therefore, we aimed to investigate the relationship between spinal posture and mobility to respiratory muscle strength and pulmonary functions in breast cancer patients who have completed their treatment METHODS: This cross-sectional study included 38 female breast cancer surgery survivors. Participants underwent the following evaluations: Chest wall mobility with a tapeline; postural assessments (spinal curvature, spinal mobility, and spinal inclination) with a non-invasive, computer-assisted electromechanical device; and pulmonary function test and respiratory muscle strength with a portable digital spirometer device. The relationship between spinal posture and mobility to respiratory muscle strength and pulmonary functions was analyzed by the bivariate correlation analysis. Increased thoracic curvature angle was associated with decreased FEV1 (r=-0.360, p=0.026) and decreased subcostal mobility (r=-0.385, p=0.017), and the increase in thoracic frontal mobility was associated with decrease in PEF (r=-0.342, p=0.036). Increased lumbar mobility was associated with increased FVC (r=0.324, p=0.047), and increased total spinal inclination mobility was associated with decreased MIP (r=-0.396, p=0.017). Chest wall mobility was associated with postural assessments at varying rates (the r value ranged from -0.357 to 0.661, p<0.05). The changes in spinal posture and mobility of women who have undergone unilateral breast cancer surgery were associated with respiratory parameters and thoracic cage mobility. These patients' spinal posture and mobility should be taken into account in conjunction with respiratory functions for a comprehensive assessment.

Mitochondrial function and oxidative stress in isolated peripheral blood mononuclear cells and trastuzumab-induced cardiotoxicity: a prospective longitudinal study

Abstract Introduction Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2), is believed to cause cardiotoxicity through mitochondrial dysfunction and oxidative stress. Although peripheral blood mononuclear cells (PBMCs) could represent systemic oxidative stress, they are also involved in trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity. The usefulness of isolated PBMCs in the assessment of trastuzumab-induced cardiotoxicity remains uncertain. Purpose We aimed to determine the temporal changes of mitochondrial function and oxidative stress in isolated PBMCs, and cardiac function in breast cancer patients receiving sequential doxorubin and trastuzumab treatment. Methods Fourteen HER-2 positive breast cancer patients with apparently normal cardiac function at baseline were recruited from September 1, 2020 to August 31, 2022. After breast surgery, all patients received doxorubicin (60 mg/m²) and cyclophosphamide (600 mg/m²) every 3 weeks for 4 cycles, followed by trastuzumab (8 mg/kg loading then 6 mg/kg) every 3 weeks for 18 cycles. Adjuvant paclitaxel (175 mg/m²) every 3 weeks for 4 cycles was an additional treatment in patients with positive lymph node(s). Echocardiography and blood samples were collected at baseline, cycle 4 of doxorubicin chemotherapy, every 3 months during trastuzumab treatment and &amp;gt;1 month after treatment. Seahorse extracellular flux analyzer was used to determine mitochondrial oxygen consumption, and MitoSox/MitoTracker staining to determine oxidative stress in isolated PBMCs. Results Of 14 patients (mean age of 50.4 ±8.8 years), 2 had hypertension and 4 had hyperlipidemia. The serum troponin I levels were significantly increased during doxorubicin treatment, then gradually decreased afterward, while the serum NT-proBNP levels remained statistically unchanged (Figure 1A and B). The numerical reduction of ejection fraction was remarked during the treatment, however there was no clinical cardiac dysfunction (Figure 1C). Subclinical cardiac dysfunction, defined as a &amp;gt;15% relative reduction in global longitudinal strain (GLS), was observed in 9 of 14 patients during trastuzumab treatment (Figure 1D). Mitochondrial oxidative stress in isolated PBMCs, although unchanged during doxorubicin treatment, was gradually increased during trastuzumab treatment (Figure 2A and B). Mitochondrial proton leak was also increased, while oxygen consumption and ATP production remained unchanged (Figure 2C and D). After treatment completion, cardiac function, as well as mitochondrial oxidative stress, tended to improve. Interestingly, there was a strong positive correlation between mitochondrial oxidative stress at baseline and maximum GLS reduction during treatment (r=0.811, p=0.001). Conclusions Mitochondrial oxidative stress in isolated PBMCs could be a potential marker for the evaluation and prediction of trastuzumab-induced cardiotoxicity. Further studies are warranted.Figure 1Figure 2

The right ventricle is not spared by the cardiotoxic effects of chemotherapy for breast cancer. Results of SAFE trial

Abstract Functional abnormalities of the right ventricle(RV) have been demonstrated in cancer patients receiving anthracyclines and trastuzumab. AHA/ACC 2022 guidelines for heart failure recommend angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers for asymptomatic LV dysfunction. It would be important to determine whether these neurohormonal modulators are beneficial for the RV as well. Design The SAFE trial (NCT: 2236806) is a four-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study. Patients with breast cancer were recruited between July 2015 and June 2020, and considered eligible if they had indicated primary or postoperative systemic chemotherapy with an anthracycline-based egimen. Patients with known cardiovascular disease or with high-risk features were excluded. Cardioprotective therapy [bisoprolol(B), Ramipril(R), or B+R], or placebo(P) were administered for 1 year since the initiation of chemotherapy or until the end of trastuzumab therapy in the case of HER2-positive patients. The drugs were systematically titrated up to the target daily dose of B (5 mg OD) and R (5 mg, OD) if tolerated. The primary endpoint was defined as the detection of any subclinical impairment (worsening ≥10%) in echocardiographic 3-dimensional left ventricular ejection fraction(3DLVEF) and global longitudinal strain(GLS) at the end-of-therapy (EOT) and at a 2-year follow-up (EOF). Echocardiographic measures of RV function (diastolic basal diameter, fractional area change(FAC), tricuspid annular plane systolic excursion(TAPSE), tissue Doppler-derived tricuspid lateral annular systolic wave velocity(S’RV) were analyzed. Results 262 women (median age, 48 years; range, 24-75 years) were enrolled and treated. We analyzed 222 patients who had completed the pre-planned cardiological assessment at 24 months. Baseline demographic, tumor, and cardiovascular profiles were similar between arms. All patients received at least 1 cycle of anthracyclines (range 1-6) and 97% at least three cycles; 217 patients received taxane, and 77 adjuvant trastuzumab. Forty-nine patients were treated with neoadjuvant chemotherapy, 154 with adjuvant endocrine therapy, and 124 had postoperative radiation therapy. At EOF 3DLVEF decreased by -10.5% in the P arm, by -3.0%, -2.4%, and -3.6% in the R, B, and R+B arms, respectively (P&amp;lt;0.001). At EOF GLS decreased by -13.1% in the P arm, by -3.6%, -3.0%, and -4.2% in the R, B, and R+B arms, respectively (P&amp;lt;0.001). At EOF the RV diameter increased by 6.7%, and FAC, TAPSE, and S’RV reduced by 10.5%, 9.6%, and 12.2%, respectively, in the P arm. In the drug arms, the changes in RV diameter, FAC, TAPSE, and S’RV were significantly less (Table and Figure). Conclusion Chemotherapy causes similar damage to the left and right ventricular function in breast cancer patients. Cardioprotective therapy significantly reduced both LV and RV damage in the low-risk patients of the SAFE study.TableFigure