Global and Regional Longitudinal Strain Reduction in Breast Cancer Patients After First Chemotherapy Cycle With Fluorouracil, Adriamycin, and Cyclophosphamide Regimen

Background: The role of nitric oxide is still unclear in advanced breast cancer patients undergoing adjuvant chemotherapy. This study was undertaken to investigate the effect of chemotherapy on serum nitric oxide levels in advanced stage breast cancer patients.Methods: In this observational study, clinically and histopathologically proven sixty female patients with advanced stage breast cancer were included. According to Tumor-Node-Metastasis (TNM) classification, patients were further grouped as stage III and stage IV. Thirty healthy and age-matched female controls were selected for comparison. Blood was collected from healthy controls and from breast cancer patients after surgery prior to chemotherapy and after three weeks of administration of first adjuvant chemotherapy cycle. Serum nitric oxide levels were measured by spectrophotometric method.Results: Significantly higher concentrations of serum nitric oxide were observed in breast cancer patients before chemotherapy in stage III (p<0.0001) and stage IV (p<0.0001) of the disease as compare to concentrations in healthy controls. The serum levels of nitric oxide were significantly decreased in stage III as well as stage IV of breast cancer patients after three weeks of receiving first adjuvant chemotherapy cycle as compare to levels before chemotherapy (p<0.0001), however serum nitric oxide levels were higher in stage III (p=0.0036) and stage IV (p<0.0001) of the disease as compare to healthy controls.Conclusions: Chemotherapy drug administration causes decrease in serum nitric oxide levels in advanced stages of breast cancer patients. Monitoring serum nitric oxide levels could be used to predict patients’ response to chemotherapy treatment in breast cancer.

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Association between Left Ventricular Global Longitudinal Strain and Six Minute Walk Test Before and After Chemotherapy with Anthracycline in Breast Cancer Patients

International Journal of ChemTech Research ◽

10.20902/ijctr.2018.110306 ◽

2018 ◽

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Longitudinal Strain ◽

Global Longitudinal Strain ◽

Left Ventricular ◽

Walk Test ◽

Breast Cancer Patients ◽

Six Minute Walk Test ◽

Before And After ◽

Minute Walk

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Phase Ib Studies of Benegrastim in Chinese Women with Breast Cancer Receiving Myelotoxic Chemotherapy

Blood ◽

10.1182/blood.v126.23.4601.4601 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4601-4601

Author(s):

Junning Cao ◽

Zhongyu Yuan ◽

Cheng Huang ◽

Dongmei Ji ◽

Rujun Peng ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Research Funding ◽

Chinese Women ◽

Dose Finding ◽

Chemotherapy Cycle ◽

Severe Neutropenia ◽

Dependent Manner ◽

Breast Cancer Patients ◽

Dose Dependent

Abstract Neutropenia is common in patients receiving myelotoxic chemotherapy. BenegrastimTM(F-627), a recombinant human G-CSF dimer, is an once-per-cycle therapy for prophylactic neutropenia in cancer patients after chemotherapy. Two phase I dose finding studies of benegrastim were conducted in Chinese women with stage I-IV breast cancer receiving myelotoxic chemotherapy. The aims of the studies were to evaluate the safety profile and pharmacokinetics (PK) and pharmacodynamics (PD) properties of benegrastim. In the first study, a total of 18 patients were enrolled to receive 3 sequential dose levels of benegrastim at 80, 240 and 360 µg/kg (n=6). The patients received epirubicin/cyclophosphamide (EC) chemotherapy on day one. Benegrastim was administered to patients on day 3 by SC injection once per chemotherapy cycle for up to 4 cycles. In the second study, 15 patients were sequentially assigned to 240 µg/kg (n=7) and 320 µg/kg (n=8) of benegrastim. These patients received doxorubicin, docetaxel and cyclophosphamide (TAC) on day one, benegrastim was administered on day 2 by SC injection for up to 6 cycles. The PK/PD properties of benegrastim were evaluated in cycle one and cycle three. Benegrastim was well tolerated in both clinical studies. The treatment emergent adverse events related to benegrastim were back pain, arthralgia, musculoskeletal pain, and rash, commonly seen in rhG-CSF therapy. The PK/PD result in patients receiving TAC in the first chemotherapy cycle is shown in Fig 1. Dose-dependent benegrastim exposure and ANC increase were demonstrated in these two clinical trials. In breast cancer patients receiving EC or TAC, benegrastim showed a non-linear pharmacokinetics. Benegrastim shortened the duration of neutropenia post chemotherapy in a dose dependent manner. In conclusion, benegrastim may provide an alternative approach to manage neutropenia, especially, severe neutropenia in patients after chemotherapy. Figure 1. PK/PD of F-627 (benegrastim) in Chinese breast cancer patients receiving TAC in the first chemotherapy cycle. Figure 1. PK/PD of F-627 (benegrastim) in Chinese breast cancer patients receiving TAC in the first chemotherapy cycle. Disclosures Cao: Generon (Shanghai) Corporation Ltd.: Research Funding. Yuan:Generon (Shanghai) Corporation Ltd.: Research Funding. Huang:Generon (Shanghai) Corporation Ltd.: Employment. Ji:Generon (Shanghai) Corporation Ltd.: Research Funding. Peng:Generon (Shanghai) Corporation Ltd.: Research Funding. Yan:Generon (Shanghai) Corporation Ltd.: Employment. Tang:Generon (Shanghai) Corporation Ltd.: Employment.

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Clinical outcomes of chemotherapy-induced subclinical left ventricular systolic dysfunction among breast cancer patients detected using echocardiographic global longitudinal strain

European Heart Journal ◽

10.1093/ehjci/ehaa946.3264 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

J.G.G Manaloto ◽

M.K Cruz-Tan ◽

R.H Tiongco ◽

R.M Jimenez ◽

G.H Cornelio

Keyword(s):

Breast Cancer ◽

Heart Failure ◽

Cancer Patients ◽

Clinical Outcomes ◽

Longitudinal Strain ◽

Systolic Dysfunction ◽

Global Longitudinal Strain ◽

Left Ventricular ◽

Breast Cancer Patients ◽

All Cause Mortality

Abstract Background Echocardiographic global longitudinal strain (GLS) detects early subclinical left ventricular (LV) systolic dysfunction, before the occurrence of a decreased LV ejection fraction. However, our local data is lacking to determine its impact to clinical outcomes. Purpose The study aimed to determine the clinical outcomes of breast cancer patients who developed subclinical LV systolic dysfunction as determined by an abnormal GLS post-chemotherapy. Methods This retrospective cohort study included 99 breast cancer patients who underwent anthracycline and/or HER-2 receptor inhibitor chemotherapy from January 1, 2016 to December 31, 2018 in a single tertiary hospital. Clinical outcomes of all-cause mortality and overt heart failure were compared between those with normal and abnormal GLS post-chemotherapy. Results The prevalence of subclinical LV systolic dysfunction was 18%, wherein 28% of them had subsequent overt heart failure, and 33% expired. Abnormal GLS occurred at a mean 3.5 months (range 1–8 months) after initiation of chemotherapy and at 8 months (range 6–10 months) after the entire chemotherapy sessions. Development into heart failure was observed at a mean of 6.7 months (range 4–12 months) after occurrence of abnormal GLS. Hypertension and age >56 years were determined to be risk factors. Beta-blockers, ACE inhibitors and statins seemed to be non-protective in our cohort. Abnormalities in GLS were observed at a mean dose of 260 mg/m2 of epirubicin, lower than the dose described as high risk in the literature (600 mg/m2 for epirubicin). In trastuzumab, abnormal GLS occurred as early as 1 month after initiation. LVEF had no significant change within 2 months (p=0.56), but was significantly lower within 12 months post-chemotherapy (p=0.005). All-cause mortality was 3-fold higher (RR=3.00; p=0.02), and the risk to develop heart failure was 4 times higher (RR=4.74; p=0.008) in those with abnormal GLS. Conclusion The development of abnormal GLS post-chemotherapy was associated with subsequent development of overt heart failure and increased all-cause mortality. Abnormal GLS occurred at lower doses of epirubicin and as early as 1 month after initiating trastuzumab. We recommend echo surveillance with GLS monitoring beginning >250 mg/m2 with anthracycline (and after 1–2 months of Trastuzumab), and to repeat at 1–2 months and 9–12 months post-chemotherapy. Funding Acknowledgement Type of funding source: None

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Fully automated and comprehensive MRI-based left-ventricular contractility analysis in post-chemotherapy breast cancer patients

British Journal of Radiology ◽

10.1259/bjr.20190289 ◽

2020 ◽

Vol 93 (1105) ◽

pp. 20190289

Author(s):

Julia Kar ◽

Michael V. Cohen ◽

Samuel A. McQuiston ◽

Maria S. Figarola ◽

Christopher M. Malozzi

Keyword(s):

Breast Cancer ◽

Steady State ◽

Cancer Patients ◽

Healthy Subjects ◽

Longitudinal Strain ◽

Steady State Free Precession ◽

Left Ventricular ◽

Free Precession ◽

Breast Cancer Patients ◽

Basal Diameter

Objective: This study investigated the occurrence of cardiotoxicity-related left-ventricular (LV) contractile dysfunction in breast cancer patients following treatment with antineoplastic chemotherapy agents. Methods: A validated and automated MRI-based LV contractility analysis tool consisting of quantization-based boundary detection, unwrapping of image phases and the meshfree Radial Point Interpolation Method was used toward measuring LV chamber quantifications (LVCQ), three-dimensional strains and torsions in patients and healthy subjects. Data were acquired with the Displacement Encoding with Stimulated Echoes (DENSE) sequence on 21 female patients and 21 age-matched healthy females. Estimates of patient LVCQs from DENSE acquisitions were validated in comparison to similar steady-state free precession measurements and their strain results validated via Bland–Altman interobserver agreements. The occurrence of LV abnormalities was investigated via significant differences in contractility measurements (LVCQs, strains and torsions) between patients and healthy subjects. Results: Repeated measures analysis showed similarities between LVCQ measurements from DENSE and steady-state free precession, including cardiac output (4.7 ± 0.4 L, 4.6 ± 0.4 L, p = 0.8), and LV ejection fractions (59±6%, 58±5%, p = 0.2). Differences found between patients and healthy subjects included enlarged basal diameter (5.0 ± 0.5 cm vs 4.4 ± 0.5 cm, p < 0.01), apical torsion (6.0 ± 1.1° vs 9.7 ± 1.4°, p < 0.001) and global longitudinal strain (−0.15 ± 0.02 vs. -0.21 ± 0.04, p < 0.001), but not LV ejection fraction (59±6% vs. 63±6%, p = 0.1). Conclusion: The results from the statistical analysis reveal the possibility of LV abnormalities in the post-chemotherapy patients via enlarged basal diameter and reduced longitudinal strain and torsion, in comparison to healthy subjects. Advances in knowledge: This study shows that subclinical LV abnormalities in post-chemotherapy breast cancer patients can be detected with an automated technique for the comprehensive analysis of contractile parameters.

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