Dysfunction 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.

The additional value of myocardial T1ρ mapping to T1 and T2 mapping for predicting subsequent cancer therapy-related cardiac dysfunction in breast cancer patients who received anthracyclines with/without trastuzumab

ObjectivesWe aimed to describe changes in parameters derived from myocardial T1ρ, T1, and T2 mapping and assess whether incorporating T1ρ mapping improves the predictive performance of T1 and T2 mapping for subsequent cancer therapy-related cardiac dysfunction (CTRCD) in breast cancer patients treated with anthracyclines with/without trastuzumab. MethodsFrom March 2021 to May 2023, 82 participants with breast cancer treated with anthracyclines with/without trastuzumab were prospectively recruited. Cardiac magnetic resonance was performed at baseline, 3 and 6 months in relation to baseline. T1ρ, T1 and T2 values were measured and compared by repeated measures analyses of variance. Logistic regression and receiver operating characteristic analysis were used to assess the performance in predicting subsequent CTRCD. ResultsNineteen (23.17 %) participants developed CTRCD. T1ρ and T1 values progressively increased over time (all p < 0.001), while T2 values increased at 3 (p < 0.001 and p = 0.002, respectively) and 6 months (all p < 0.001) compared to baseline in both the CTRCD (+) and CTRCD (−) groups. The changes in T1ρ (OR, 3.892, p = 0.003) and T1 (OR, 1.082, p = 0.002) from baseline to 3 months were associated with subsequent CTRCD. The combination of the changes in T1ρ and T1 from baseline to 3 months obtained an improved area under the curve of 0.853. ConclusionT1ρ, T1 and T2 increased after treatment of anthracyclines with/without trastuzumab. Myocardial T1ρ mapping provides additional predictive value to T1 mapping for subsequent CTRCD in breast cancer patients who received anthracyclines with/without trastuzumab. Clinical relevance statementMyocardial T1ρ mapping offers additional predictive value to T1 and T2 mapping for subsequent CTRCD in breast cancer patients who received anthracyclines with/without trastuzumab. This may facilitate accurate prediction of cardiotoxicity and personalized treatment decision making in breast cancer.

Redefining anthracycline-related subclinical cardiotoxicity: 'Absolute' and 'relative' change in longitudinal strain.

Anthracycline chemotherapy (AC) for breast cancer can cause cancer therapy-related cardiac dysfunction (CTRCD) with resultant heart failure, traditionally defined as a reduction in left ventricular (LV) ejection fraction on echocardiography. In recent years, global longitudinal systolic strain (GLS) has been used to identify subclinical cardiac dysfunction prior to development of overt CTRCD. Recent harmonized guidelines have incorporated GLS into definitions for CTRCD to identify cardiac dysfunction and inform decisions regarding cardioprotective strategies. We evaluated subclinical dysfunction in breast cancer patients treated with AC and determined the echocardiographic and patient factors associated with significant GLS changes. One hundred fourteen HER2 negative patients treated with AC were prospectively recruited and underwent serial echocardiograms (LVEF and LVGLS) at three time points (prior to AC, 3months, and 1year). CTRCD was defined as an asymptomatic reduction in LVEF of 10% or symptomatic drop of 5% to LVEF <53%. Subclinical LV dysfunction was defined as a reduction of ≥10% in GLS compared with baseline, recognizing that this cut off identified an 'at risk cohort' rather than patients with established CTRCD. No participant demonstrated CTRCD by reduction in LVEF. Forty-three patients (38%) demonstrated a ≥10% relative reduction in GLS at 12months; 20/43 (47%) had a reduced absolute GLS to <16%, and were older, had hypertension, increased LV mass, lower baseline e' velocity and GLS. GLS ≥20.5% at baseline yielded a sensitivity of 79% and specificity of 87% for a normal GLS (i.e., ≥16%) at 1year despite a ≥10% reduction from baseline. We present a stepwise evaluation for subclinical LV dysfunction using both a relative reduction in GLS combined with an absolute reduction in GLS. We believe our findings may re-stratify patients with a high baseline GLS into a lower risk group despite transient relative GLS decrements ≥10%.

Assessment of Chemotherapy-Induced Cardiac Dysfunction in Breast Cancer Patients: A Prospective Study.

Background Advances in cancer treatment have markedly improved survival rates but have also heightened morbidity due to treatment-related side effects. Despite this, the literature remains scarce on predicting the incidence of acute cardiac toxicity resulting from chemotherapy. We conducted a prospective evaluation to assess the incidence, timing, clinical correlates, global longitudinal strain (GLS), and response to heart failure (HF) therapy in patients experiencing cardiotoxicity. Aims and objectives Our study aimed to assess the cardiovascular complications of cancer therapy in breast cancer patients, with particular emphasis on therapy-related cardiac dysfunction. Materials and methods We conducted a prospective observational study to detect chemotherapy-related cardiac dysfunction (CTRCD) in breast cancer patients attending the outpatient department (OPD) or admitted to Dayanand Medical College and Hospital (DMCH), Ludhiana, Punjab, between March 1, 2020, and October 31, 2021. We assessed left ventricular ejection fraction (LVEF) at baseline, mid-chemotherapy, and post-chemotherapy. Patients who developed left ventricular dysfunction (LVD) had their chemotherapy regimen modified and were initiated on HF therapy. Results Ninety-seven patients (mean age: 50.74±10.30 years) were enrolled and categorized into the LVD group (n=13) and non-LVD group (n=84). CTRCD developed in 13 patients (13.4%). Patients with estrogen receptor (ER) positive, progesterone receptor (PR) positive, and human epidermal growth factor receptor 2 (HER2) positive status, as well as those in cancer stages III and IV, are at higher risk of developing LV dysfunction. Among the 13 patients, 10 (77%) experienced complete recovery, while three (23%) had partial recovery. Markers for partial recovery included cancer stages III-IV, younger age, lower body mass index (BMI), lower radiotherapy dosage, lower mean chemotherapy dosage, and left breast involvement. Conclusion Our findings suggest that acute cardiotoxicity is not linked to the cumulative dose of anthracyclines. Early detection, modification of chemotherapy regimens, and prompt initiation of CTRCD therapy can lead to substantial recovery of cardiac dysfunction.

Arterial Stiffness May Predict Subsequent Cancer Therapy-Related Cardiac Dysfunction in Breast Cancer Patients

Cancer therapy-related cardiac dysfunction (CTRCD) is still a serious problem. Existing risk scores are insufficient for risk classification, especially in low and medium-risk patients. This study aims to evaluate if arterial stiffness (AS) measurement, which is associated with most of the known risk factors, can be a useful parameter for predicting subsequent CTRCD in patients with breast cancer (BC). Patients with BC were included in the study. All patients’ AS parameters such as pulse wave velocity (PWV), augmentation index (AIx), augmentation pressure (AP), and echocardiographic parameters were obtained before treatment. During treatment, echocardiographic follow-up with routine parameters and left ventricle global longitudinal strain (LVGLS) were measured. Patients were evaluated on whether CTRCD occurred or not. A total of 67 patients were analyzed. The mean age of the study population was 54.9 ± 11 years. Baseline characteristics were similar except for age. No CTRCD diagnosis was obtained according to left ventricle ejection fraction (LVEF) reduction, but 18 patients (26.8%) developed CTRCD regarding the decline in LVGLS. Left ventricle hypertrophy and diastolic dysfunction were more frequent in patients with CTRCD (p = 0.016 and p = 0.015, respectively). PWV, AIx, and AP as AS parameters were significantly higher in patients with CTRCD, but Alx@75 were not (p = 0.005, p = 0.034, p = 0.008, p = 0.077, respectively). A positive correlation between PWV and a decreased percent in LVGS (R = 0.607, p < 0.001) was observed. ROC curve analyses revealed an AUC of 0.747 (p = 0.02, 95% CI 0.632–0.832) for PWV. A PWV value of 9.2 m/s predicted CTRCD with 94% sensitivity and 73% specificity. AS measurement may be useful for predicting CTRCD in patients with low to medium-risk BC.Graphical

Cognitive-enhanced eHealth psychosocial stepped intervention for managing breast cancer-related cognitive impairment: Protocol for a randomized controlled trial.

Breast cancer often leads to cancer-related cognitive impairment (CRCI), which includes both objective and subjective cognitive deficits. While psychosocial interventions benefit quality of life and distress reduction, their impact on cognitive deficits is uncertain. This study evaluates the integration of a cognitive module into a digital psychosocial intervention for breast cancer patients. In this randomized controlled trial (RCT), 88 recently diagnosed breast cancer (BC) patients will receive the ICOnnecta't program (control group) - a digital stepped intervention addressing a variety of psychosocial needs. The experimental group (n = 88) will receive ICOnnecta't plus a cognitive module. Assessments at baseline, 3, 6, and 12 months will measure the interventions' impact on cognition, emotional distress, medication adherence, quality of life, post-traumatic stress, work functioning and healthcare experience. Feasibility and cost-utility analyses will also be conducted. The cognitive module includes three levels. The first level contains a cognitive screening using FACT-Cog Perceived Cognitive Impairment (PCI). Patients with PCI <54 progress to a cognitive psychoeducational campus (Level 2) with content on cognitive education, behavioural strategies and mindfulness. Patients with persistent or worsened PCI (≥6) after 3 months move to Level 3, an online cognitive training through CogniFit software delivered twice a week over 12 weeks. This study assesses whether integrating a cognitive module into a digital psychosocial intervention improves objective and subjective cognition in breast cancer patients. Secondary outcomes explore cognitive improvement's impact on psychosocial variables. The research will contribute to testing efficacious approaches for detecting and addressing cognitive dysfunction in breast cancer patients. ClinicalTrials.gov, NCT06103318. Registered 26 October 2023, https://classic.clinicaltrials.gov/ct2/show/NCT06103318?term=serra-blasco&draw=2&rank=4.

Biomarkers and Strain Echocardiography for the Detection of Subclinical Cardiotoxicity in Breast Cancer Patients Receiving Anthracyclines.

The optimal surveillance and management strategies for breast cancer patients receiving anthracycline therapy are limited by our incomplete understanding of the role of biomarkers heralding the onset of cardiotoxicity. The purpose of this study was to determine whether there is a temporal correlation between cardiac biomarkers and subclinical left ventricular dysfunction in breast cancer patients receiving anthracycline chemotherapy. Thirty-one females between 46 and 55 years old with breast cancer treated with anthracycline chemotherapy were prospectively enrolled. Cardiac biomarkers were correlated with echocardiography with speckle tracking at baseline, post-anthracycline therapy, and 6 months post-anthracycline chemotherapy. Subclinical cardiotoxicity was defined as ≥ 10% reduction in global longitudinal strain (GLS). There was a relative reduction in left ventricular ejection fraction (LVEF) ≥ 10% in 5/30 (17%) and 7/27 (26%) patients post-anthracycline therapy and 6 months post-anthracycline therapy, respectively. Subclinical cardiotoxicity was noted in 8/30 (27%) and 10/26 (38%) patients post-anthracycline and 6 months post-anthracycline therapy, respectively. Baseline N-terminal pro B-type natriuretic peptide (NT-proBNP) was the strongest predictor of LVEF (ρ = -0.45; p = 0.019), with post-therapy NT-proBNP values illustrating similar predictive value (ρ = -0.40; p = 0.038). Interim changes in suppression of tumorigenicity 2 (ST2) and galectin-3 correlated with a 6-month change in LVEF (ρ = -0.48; p = 0.012 and ρ = -0.45; p = 0.018, for ST2 and galectin-3, respectively). Changes in galectin-3 from baseline to mid-therapy paralleled changes in GLS. NT-proBNP, ST2, and galectin-3 correlate with reduced LVEF among breast cancer patients receiving anthracycline therapy. Additional trials focusing on a cardiac biomarker approach may provide guidance in the early diagnosis and management of anthracycline-induced cardiotoxicity.

Investigating the levels of depression, anxiety, sexual disorders, and other influencing factors in breast cancer patients: Turkish radiation oncology integrative group study (12-05).

The fear of death associated with cancer and the side effects of its treatments can have a detrimental psychological impact on breast cancer patients. Early detection and support services play a crucial role in alleviating the expected symptoms of depression, anxiety, and sexual dysfunction. The objective of our study is to assess the levels of depression, anxiety, and sexual dysfunction in breast cancer patients, as well as identify the factors that influence these conditions. The study involved 329 voluntarily participating breast cancer patients who had undergone surgery and were in the follow-up stage. Data were collected from 8 different centers after obtaining ethical approval. The assessment utilized tools such as the Sociodemographic Information Form, Beck Depression and Anxiety Scale, and Arizona Sexual Experiences Scale. Data analysis was performed using SPSS 20. The study included 329 breast cancer patients in the follow-up stage post-surgery. Their average age was 52.7 years (range: 27-83). Results indicated that 33.1% experienced moderate to severe depression, 18.2% reported severe anxiety, and 82.7% scored above 11 on the sexual scale. Factors linked to higher scores were mastectomy, surgical dissatisfaction, insufficient information on sexual side effects, and comorbidities like smoking and diabetes. The study emphasizes the importance of closely monitoring anxiety, depression levels, and sexual side effects in breast cancer treatment. It underscores the need to focus not only on reducing mortality rates but also on supporting patients' psychological and sexual well-being, ultimately improving their overall quality of life.

Role of Statin Therapy in Prevention of Anthracycline-Induced Cardiotoxicity: A Three Dimentional Echocardiography Study

Recent advances in the treatment of breast cancer have resulted in improved overall cancer survival; however, cancer therapy related cardiac dysfunction is considered a major adverse effect of several chemotherapeutic agents, particularly anthracyclines. Hence, there is a need to develop proper cardioprotective strategies to limit myocardial injury following chemotherapy. To evaluate the effect of statin therapy on prevention of anthracycline- induced cardiotoxicity in female patients with breast cancer. The current study is a prospective, randomized, single-blind, placebo-controlled trial in which we enrolled a total of 110 female patients with newly diagnosed breast cancer who received anthracycline based chemotherapy. Patients were randomly assigned in 1:1 ratio into two groups, study group in which patients received 40 mg of oral atorvastatin and control group in which patients received placebo. A comprehensive echocardiographic examination was performed to all patients prior to receiving the chemotherapy and after 6 months, assessment of LV ejection fraction was done by 3D-echocardiography. All echocardiographers were blinded to all the patients' characteristics and assignment to either group. The mean age of patients assigned to the control group was 49.8±10.51 years old, while patients assigned to the intervention group had mean age of 47.84± 9.16 years old, both the control group and the intervention group were similar in demographic data and baseline clinical characteristics. There was a highly significant difference between the two groups regarding both the absolute LVEF assessed by 3D- echocardiography at 6 months and the percentage of change compared to baseline values, patients assigned to the control group had mean LVEF of 52.92% at 6 months with percentage of change reaching -7.06%, while those assigned to the intervention group had mean LVEF reaching 56.22% at 6 months with a percentage of change reaching -3.64% (P-value: 0.008 and 0.004 for the absolute value and percentage of change respectively). There was a significant difference between the two groups regarding incidence of development of cancer therapy related cardiac dysfunction (CTRCD); defined as drop in LVEF more than 10% and to a value below 53% assessed by 3D echocardiography, among the control group 15 patients (30%) developed CTRCD after 6 months from starting Anthracyclines based chemotherapy, while, among the intervention group only 6 patients (12%) developed CTRCD. (P-value= 0.027) CONCLUSION: Prophylactic use of atorvastatin may prevent the development of cancer therapy related cardiac dysfunction in breast cancer patients receiving anthracycline based chemotherapy.

Correlation between Thyroid Radiation Dose and Thyroid Function after Adjuvant Hypofractionated Locoregional Radiotherapy in Breast Cancer Patients

Radiotherapy (RT) is used quite often among breast cancer patients, and because these patients now live longer than they used to, long-term treatment-related adverse effects, such as hypothyroidism, are becoming increasingly relevant. Radiation-induced hypothyroidism is a late side effect of radiation to the thyroid gland, which could develop months to years after radiotherapy. However, there is no sufficient data on hypothyroidism in patients with breast cancer who receive locoregional RT, which usually affects a portion of the thyroid gland. In this prospective study, we tried to correlate between the radiation dose received by the thyroid gland and the incidence of thyroid dysfunction in breast cancer patients treated with hypofractionated locoregional radiotherapy, as well as establishing potential planning objectives that could help in sparing the thyroid gland. Our study included 109 women who received 3-D conformal loco-regional breast radiotherapy, these patients had normal thyroid function prior to start of radiotherapy. Patients had follow-up thyroid function tests 6 months after finishing radiotherapy. Based on dose volume histograms (DVH), the percentages of the thyroid volume, and ipsilateral thyroid lobe, receiving 5, 10, 15, 20, 25, 30, 35, and 40 Gy (V5, V10, V15, V20, V25, V30, V35, and V40 respectively), in addition to the mean and maximum thyroid doses, were estimated. Follow-up assessment of thyroid function and statistical analysis unveiled incidence of radiotherapy induced hypothyroidism to be 8.3%. Possible risk factors included high maximum radiation dose and V40 to the thyroid gland and the ipsilateral thyroid lobe, as well as high mean dose and smaller volume of the ipsilateral thyroid lobe. The likelihood of hypothyroidism was significantly increased with V40 of >5% of the thyroid gland, and V40 of >11% of the ipsilateral thyroid lobe. Further study is recommended for larger populations and longer follow-up periods.

Abstract P5-08-08: Ultrasound-guided injection with or without rehabilitation exercise in breast cancer survivors with sub-acromion-deltoid bursitis: a pilot randomized clinical study

Abstract BACKGROUND: Due to the increasing overall survival of breast cancer (BC) patients, a growing interest has been raised in the current literature on disabling consequences of cancer and its treatment [1,2]. In particular, after radical surgery for BC, patients might frequently be affected by functional limitation of the shoulder joint, potentially related to the immobilization, surgical scar tensions, axillary web syndrome, subpectoral prostheses or expanders, or peripheral nerve damage [3]. In this scenario, several challenges are still open in the therapeutic approach to this disabling condition and the optimal management of shoulder dysfunction in breast cancer patients is far from being fully characterized. Therefore, the aim of this study was to assess the effects of a comprehensive rehabilitation program including ultrasound-guided injection of the sub-acromion deltoid bursa (SAD) followed by a rehabilitation exercise protocol in terms of feasibility, pain relief, upper limb function, quality of life, and safety. METHODS: In this study, we recruited consecutive breast cancer women referring to a Physical Medicine and Rehabilitation in Northern Italy and suffering from SAD bursitis in the absence of tendon lesions. Patients were assessed for eligibility and subsequently randomly assigned 1:1 to two groups. Group A received ultrasound-guided percutaneous injection of the SAD bursa (lidocaine and triamcinolone acetate) followed by a rehabilitation exercise program of 5 sessions lasting 1 hour each., while Group B received ultrasound-guided percutaneous injection only. Patients were assessed at baseline (T0), after a week (T1), and after 3 months (T2). The outcomes were numerical pain rating scale (NPRS), handgrip strength (HGS) test, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the Oxford Shoulder Score (OSS), Global Perceived Effect (GPE), and safety. RESULTS: Thirty-seven patients were enrolled and randomly assigned to Group A (n=19; mean age: 56.05 ± 10.30 years; body mass index (BMI): 23.58 ± 2.79 kg/m2) and Group B (n=18; mean age: 58.39 ± 12.09 years; BMI: 22.72 ± 3.16 kg/m2). No major or minor adverse events were reported after this multidisciplinary intervention. Statistically significant within-group differences were found in both groups in terms of NPRS after the treatment (p &amp;lt; 0.05) and after the follow-up (p &amp;lt; 0.05). The between-group analysis showed significant differences in pain intensity (NRS: 2.16 ± 1.39 vs 4.78 1.77; p &amp;lt; 0.05), isometric muscle strength (25.11 3.20 vs 20.33 4.92; p&amp;lt; 0.001), shoulder function (OSS: 17.00 3.27 vs 33.11 6.471; p&amp;lt; 0.0001), and EORTC QLQ-C30 (Functional subscale: 88.74 7.71 vs 77.67 13.64; p=0.017; Symptom subscale: 11.43 8.56 vs 19.61 13.72; p=0.048; Global Health subscale: 79.36 13.72 vs 70.56 8.26; p=0.022) of the after the follow-up. However, no significant differences (p &amp;gt; 0.05) were reported at T1. CONCLUSION: Our findings showed that a comprehensive rehabilitation approach including ultrasound-guided injection combined with rehabilitation exercise might be safe, well-tolerated, and effective in breast cancer patients with SAD bursitis. These data emphasized the positive role of an interdisciplinary rehabilitation management in pain management and improving overall well-being of breast cancer patients. Further studies with larger samples and longer follow-ups are needed to confirm our data. REFERENCES: 1. Nardin S et al. Breast Cancer Survivorship, Quality of Life, and Late Toxicities. Front Oncol 2020, 10, 864. 2. D’Egidio V et al. Counseling interventions delivered in women with breast cancer to improve health-related quality of life: a systematic review. Qual Life Res 2017, 26, 2573-2592, doi:10.1007/s11136-017-1613-6. 3. Hidding JT et al. Treatment related impairments in arm and shoulder in patients with breast cancer: a systematic review. PLoS One. 2014 May 9;9(5):e96748. Citation Format: Lorenzo Lippi, Alessandro de Sire, Arianna Folli, Francesco D’Abrosca, Alessio Turco, Giuseppina Bonizzi, Nicola Fusco, Marco Invernizzi. Ultrasound-guided injection with or without rehabilitation exercise in breast cancer survivors with sub-acromion-deltoid bursitis: a pilot randomized clinical study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-08.

Neoadjuvant chemotherapy modulates exhaustion of T cells in breast cancer patients.

Breast cancer is the leading cause of cancer deaths in women worldwide. It has been observed that the incidence of breast cancer increases linearly with age after 45, which suggest a link between cancer, aging, and senescence. A growing body of evidence indicates that the immunosuppressive tumor network in breast cancer patients can lead to T-cell exhaustion and senescence. Cytotoxic chemotherapy is a common treatment for many cancers, and it is hypothesized that its efficacy may be related to immune activation. However, the effects of neoadjuvant chemotherapy on T-cell dysfunction in breast cancer patients are not fully understood. This study aimed to evaluate the impact of neoadjuvant chemotherapy on the expression of exhaustion and senescence markers in T cells in women with breast cancer. Our results showed that T cells from breast cancer patients have a reduced ability to respond to stimulation in-vitro and an increased expression of senescence and exhaustion-associated markers, such as TIM-3, LAG3, and CD57. Furthermore, we found that neoadjuvant chemotherapy has an immunomodulatory effect and reduces the expression of exhaustion markers. Our observations of the immune phenotype of T cells during neoadjuvant chemotherapy treatment highlight its ability to stimulate the immune system against cancer. Therefore, monitoring the response of T cells during chemotherapy may enable early prediction of clinical response.

Evaluation of the Effect of Carvedilol in Preventing Right Ventricular Dysfunction in Breast Cancer Patients Receiving Anthracycline.

Today, it has been shown that it is possible for right ventricular (RV) wall motion abnormalities or RV functional disorders to occur during cancer treatment. Now, considering the effect of carvedilol on beta 1, 2, and alpha receptors and its antioxidant properties, it seems that it can prevent RV abnormalities. Therefore, the aim of this study was to investigate the possible protective effects of carvedilol in preventing RV dysfunction in patients with breast cancer treated with anthracyclines. The present single-blind clinical trial study was performed on 23 patients with breast cancer that 12 of them received only the anthracycline antineoplastic doxorubicin (Adriamycin®) chemotherapy (control group) and 11 patients received carvedilol in addition to anthracycline. To evaluate the effect of carvedilol, patients underwent transthoracic echocardiography before intervention and 2 weeks after the end of treatment with anthracyclines. The two parameters of RV ejection fraction and RV fractional area change in the carvedilol group with a mean of 66.41% ± 8.10% and 51.85% ± 6.89% were slightly higher than the control group with a mean of 64.58% ± 6.83% and 50.48 ± 5.79%, respectively, which was not statistically significant (P > 0.05). In contrast, RV S wave tissue Doppler imaging (S-TDI) in the control group with a mean of 0.13 ± 0.02 m/s was significantly lower than the carvedilol group with a mean of 0.14 ± 0.02 m/s (P = 0.022). According to the results of the present study, the effect of using carvedilol as a preservative on improving RV function was seen compared to the control group, although this difference was not statistically significant.

Usefulness of cardiac magnetic resonance for early detection of cancer therapeutics-related cardiac dysfunction in breast cancer patients

BackgroundPrognosis of breast cancer patients has been improved along with the progress in cancer therapies. However, cancer therapeutics-related cardiac dysfunction (CTRCD) has been an emerging issue. For early detection of CTRCD, we examined whether native T1 mapping and global longitudinal strain (GLS) using cardiac magnetic resonance (CMR) and biomarkers analysis are useful. MethodsWe prospectively enrolled 83 consecutive chemotherapy-naïve female patients with breast cancer (mean age, 56 ± 13 yrs.) between 2017 and 2020. CTRCD was defined based on echocardiography as left ventricular ejection fraction (LVEF) below 53% at any follow-up period with LVEF>10% points decrease from baseline after chemotherapy. To evaluate cardiac function, CMR (at baseline and 6 months), 12‑lead ECG, echocardiography, and biomarkers (at baseline and every 3 months) were evaluated. ResultsA total of 164 CMRs were performed in 83 patients. LVEF and GLS were significantly decreased after chemotherapy (LVEF, from 71.2 ± 4.4 to 67.6 ± 5.8%; GLS, from −27.9 ± 3.9 to −24.7 ± 3.5%, respectively, both P < 0.01). Native T1 value also significantly elevated after chemotherapy (from 1283 ± 36 to 1308 ± 39 msec, P < 0.01). Among the 83 patients, 7 (8.4%) developed CTRCD. Of note, native T1 value before chemotherapy was significantly higher in patients with CTRCD than in those without it (1352 ± 29 vs. 1278 ± 30 msec, P < 0.01). The multivariable logistic regression analysis revealed that native T1 value was an independent predictive factor for the development of CTRCD [OR 2.33; 95%CI 1.15–4.75, P = 0.02]. ConclusionsThese results indicate that CMR is useful to detect chemotherapy-related myocardial damage and predict for the development of CTRCD in breast cancer patients.

Subclinical Left Ventricular Dysfunction Detected by Speckle-Tracking Echocardiography in Breast Cancer Patients Treated With Radiation Therapy: A Six-Month Follow-Up Analysis (MEDIRAD EARLY-HEART study).

BackgroundIn the case of breast cancer (BC), radiotherapy (RT) helps reduce locoregional recurrence and BC-related deaths but can lead to cardiotoxicity, resulting in an increased risk of long-term major cardiovascular events. It is therefore of primary importance to early detect subclinical left ventricular (LV) dysfunction in BC patients after RT and to determine the dose–response relationships between cardiac doses and these events.MethodsWithin the frame of the MEDIRAD European project (2017–2022), the prospective multicenter EARLY‐HEART study (ClinicalTrials.gov Identifier: NCT03297346) included chemotherapy naïve BC women aged 40–75 years and treated with lumpectomy and adjuvant RT. Myocardial strain analysis was provided using speckle‐tracking echocardiography performed at baseline and 6 months following RT. A global longitudinal strain (GLS) reduction >15% between baseline and follow-up was defined as a GLS-based subclinical LV dysfunction. Individual patient dose distributions were obtained using multi-atlas-based auto-segmentation of the heart. Dose-volume parameters were studied for the whole heart (WH) and left ventricle (LV).ResultsThe sample included 186 BC women (57.5 ± 7.9 years, 64% left-sided BC). GLS-based subclinical LV dysfunction was observed in 22 patients (14.4%). These patients had significantly higher cardiac exposure regarding WH and LV doses compared to patients without LV dysfunction (for mean WH dose: 2.66 ± 1.75 Gy versus 1.64 ± 0.96 Gy, p = 0.01). A significantly increased risk of subclinical LV dysfunction was observed with the increase in the dose received to the WH [ORs from 1.13 (V5) to 1.74 (Dmean); p <0.01] and to the LV [ORs from 1.10 (V5) to 1.46 (Dmean); p <0.01]. Based on ROC analysis, the LV-V5 parameter may be the best predictor of the short-term onset of subclinical LV dysfunction.ConclusionThese results highlighted that all cardiac doses were strongly associated with the occurrence of subclinical LV dysfunction arising 6 months after BC RT. Whether measurements of GLS at baseline and 6 months after RT combined with cardiac doses can early predict efficiently subclinical events occurring 24 months after RT remains to be investigated.

LVEF decline in relation to body composition among women treated for breast cancer: WF-97415.

10556 Background: Despite an improvement in survival from breast cancer (BC), many women experience cardiotoxicity. Left ventricular ejection fraction (LVEF) is reduced by an average of 9.7% in women receiving anthracyclines. Obesity and central adiposity at BC diagnosis may influence risk of LVEF decline. We sought to examine associations between body composition and LVEF decline in the UPBEAT (Understanding and Predicting Fatigue, Cardiovascular Decline, and Events After Breast Cancer: WF-97415) study, which was conducted in collaboration with NCI Community Oncology Research Program. Methods: The analytic cohort was comprised of 167 women treated for stage I-III BC with chemotherapy and/or radiation in the UPBEAT prospective study, in whom LVEF was obtained at baseline (pre-treatment) and 3 months. Linear regression was used to examine LVEF decline in relation to 1) waist circumference (WC) and body mass index (BMI) at baseline and 2) changes in WC and BMI during BC treatment. All models were adjusted for age and race. Results: In this cohort (mean [SD] age: 55.7 [10.8] yrs; in whom 75% were white; 19% were Black), the mean (SD) LVEF at baseline was 60.7 (6.7)% with a mean decline of 2.7 (7.2)% from baseline to 3-months. Both WC and BMI at BC diagnosis were associated with LVEF decline during follow-up (Table). For each additional inch in WC, EF decreased by 0.25% points at 3 months (P=0.024); for each additional kg/m2 in BMI, EF decreased by 0.2% points at 3 months (P=0.007). Reduced BMI during treatment was associated with LVEF decline, whereas a change in WC was not. Each kg/m2 reduction in BMI was associated with a 0.4% point decrease in LVEF (p=0.037). Anthracycline use was associated with a 1.89% point decline in LVEF at 3 months versus non-users (p=0.049). After additional adjustment for anthracycline use, baseline WC remained statistically significantly associated with LVEF decline to the same degree. Conclusions: These data show that central adiposity at BC diagnosis is associated with LVEF decline during treatment, even after controlling for anthracyclines. Loss of central adiposity was not associated with LVEF decline, whereas BMI loss during treatment was. This suggests that shifts in body composition during BC treatment, potentially via loss of muscle mass, are important to monitor in patients. Future work should examine how changes in body composition, particularly changes in skeletal muscle and adipose tissue depots, influence cardiac dysfunction in BC patients during treatment. Funding: 2UG1CA189824, R01CA199167, 2UG1CA189828. [Table: see text]

Right ventricular diastolic dysfunction in breast cancer patients undergoing chemotherapy

Abstract Funding Acknowledgements Type of funding sources: None. Right ventricular (RV) diastolic dysfunction has been recognized as an independent predictor of adverse events and mortality in a wide range of diseases (1,2). Experimental and clinical data indicate that pathophysiological factors induce the development of RV diastolic dysfunction first, and only later - systolic dysfunction (3). The aim of the study was to assess the right ventricle diastolic function in patients with breast cancer undergoing chemotherapy. Material and methods The study included 40 women receiving anthracycline-based chemotherapy for cancer, and 25 age-matched and comorbidity-matched women without cancer as a control group. RV systolic (s"t, Tei-index, and TAPSE) and diastolic (Et, At, Et/At, e"t, a"t, e"t/a"t) function parameters at baseline and after treatment were compared and evaluated. Results In cancer patients during anthracycline-based chemotherapy, no signs of cardiotoxicity were detected according to the indicators of the left ventricular ejection fraction and global longitudinal strain. Progressive decline in RV diastolic function was noted in patients receiving anticancer therapy. Et was 53.0 (46.0; 62.0) sm/sec in control, 50.0 (41.0; 53.0) sm/sec in cancer group before treatment, and 45.0 (41.0; 51.0) sm/sec after one-year treatment (p = 0.017 for trend). Et/At was 1.4 (1.28; 1.6), 1.34 (1.23; 1.58), and 1.12 (0.81; 1.35), respectively (p = 0.002 for trend). RV systolic function was without changes during treatment. TAPSE was 2.5 (2.2; 2.8) sm in control, 2.3 (2.2; 2.5) sm in cancer group before treatment, and 2.3 (2.0; 2.4) sm after one-year treatment (p = 0.091 for trend). Conclusion Patients undergoing chemotherapy experience a decline in right ventricular filling rates despite not showing clear signs of anthracycline-associated cardiotoxicity. More research is needed to indicate the clinical and prognostic significance of such changes.

Three-dimensional principal strain, twist and torsion as predictors of cancer therapeutics related cardiac dysfunction in breast cancer patients

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Research Foundation of Korea Background Breast cancer patients usually received anti-cancer chemotherapy even in the early stage. Main regimen includes anthracycline and trastuzumab which are known to have cardiotoxicity. Three-dimensional echocardiography can provide all conventional and deformational parameters in one image but its utility is limited. Methods The patients underwent adriamycin based chemotherapy and three-dimensional echocardiography before and 1 year after were included. All the analyses of 3-dimensioanl echocardiographic images were performed using 4D LV Analysis (TomTec, Unterschleissheim, Germany). Cancer therapeutics related cardiac dysfunction was defined as decrease in the value of longitudial strian more than 15 % in the follow up compared to the pre-chemotherapy exam. Results : The number of patients was 75. One patient was admitted due to symptoms related to heart failure. Multivariate logistic regression analysis showed that 3-dimensional longitudial strian measured before chemotherapy can predict CTRCD (Odds ratio; 95% confidence interval: 0.63; 0.42-0.93. p value = 0.02). Conclusion 3-dimensional deformation parameters can be used as predictors of CTRCD in breast cancer patients and it should be applied more widely in clinical settings. Abstract Figure. Usefulness as a predictor

Potential role of BRCA1 protein expression as a prognostic tissue biomarker in breast carcinoma: an immunohistochemical and clinicopathologic study from South India

Introduction. BRCA1 dysfunction is a hallmark of both hereditary and sporadic breast cancer. BRCA1 protein expression can be lost by germline mutation, somatic mutation or promoter hypermethylation. This study aimed to explore BRCA1 dysfunction in breast cancer patients by immunohistochemistry and to study its association with prognostic factors. Material and methods. BRCA1 protein expression was assessed by immunohistochemistry on formalin fixed paraffin embedded tissue blocks of 110 invasive breast carcinoma patients. Furthermore, the clinical findings and tumor features associated with BRCA1 dysfunction were characterized. Results. Reduced BRCA1 immunoreactivity was observed in 19% of breast cancer cases. Although these patients presented with aggressive tumor characteristics, statistical significance was observed only with presence of lymphovascular emboli (p &lt; 0.05). These results suggest that loss of BRCA1 protein expression is associated with an aggressive phenotype of breast carcinoma. Conclusions. Immunohistochemistry for BRCA1 protein expression in tumor tissues may provide a less expensive screening tool to identify BRCA1 dysfunction due to genetic or epigenetic alterations.

Sensitivity and specificity of strain rate for the early detection of left ventricular dysfunction in breast cancer patients receiving adjuvant treatment with adriamycin with or without trastuzumab

Abstract Background Medical literature states that a global longitudinal strain rate (GLS) &amp;lt;−19% and further reductions in relation with baseline GLS may predict long term left ventricular dysfunction in breast cancer patients receiving adjuvant treatment with Adriamycin (A) with or without trastuzumab (T). However, there is not strong evidence to support the use of this technique in daily clinical practice. Purpose To analyze the sensitivity (S) and specificity (Sp) of GLS &amp;lt;−19% or its relative 10, 15 and 20% reduction form baseline, for the early detection of left ventricular dysfunction in breast cancer patients receiving adjuvant treatment with A with or without T. Methods Patients were prospectively assessed with a cardiac echoDoppler + GLS at baseline, every 3 months during the first year and every 4 months thereafter. We assessed the S and Sp of GLS &amp;lt;−19% or its relative &amp;gt;10%, &amp;gt;15% and &amp;gt;20% reduction form baseline after treatment with A with or without T as predictors of cardiotoxicity (defined as a &amp;gt;10 percentage points decrease of left ventricular ejection fraction to a value below the lower normal limit with respect to baseline). Results 136 out of 884 patients (16%) had GLS measured at each visit: 83 patients (60%) and 53 patients (40%) treated with A or A+T respectively. Patients were followed up to 31±6 months. Mean age was 51±12 years. The table shows the baseline characteristics of both groups. 10 out of 83 patients in group A (12%) and 18 out of 53 P in group A+T (34%) developed cardiotoxicity. Baseline left ventricular ejection fraction and GLS were 61±4,7% and −20,18±2,6% in group A, and 58,7±5,8% and −19,5±2,6 post treatment. In this group, GLS S and Sp were 50 and 80%, respectively. In the group A+T, the best GLS cutoff was −19%, with a 60% sensitivity and 78% specificity. Conclusions In our non-selected cohort of patients, nor GLS or its percentage reductions along follow up predicted the reduction of left ventricular ejection fraction and the developing of cardiotoxic ventricular dysfunction in breast cancer patients receiving adjuvant treatment with A with or without T. The systematic use of this tool should be further investigated and validated at each center to help establish its usefulness in daily practice. Funding Acknowledgement Type of funding sources: None. Baseline characteristics