Breast cancer diagnosis is associated with relative left ventricular hypertrophy and elevated endothelin-1 signaling

Maayah, Zaid H.; Takahara, Shingo; Alam, Abrar S.; Ferdaoussi, Mourad; Sutendra, Gopinath; El‐Kadi, Ayman O.S.; Mackey, John R.; Pituskin, Edith; Paterson, Ian; Dyck, Jason R.B.

doi:10.1186/s12885-020-07217-1

Cited by 12 publications

(17 citation statements)

References 42 publications

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“…We recently reported that patients with cancer have relative cardiac hypertrophy prior to receiving cancer treatment, 28 and others have reported abnormal cardiac function at baseline. 29 Thus, patients with cancer may be predisposed to developing CV disease independent of treatment.…”

Section: Discussionmentioning

confidence: 92%

Incident Cardiovascular Disease Among Adults With Cancer

Paterson

Wiebe

Cheung

et al. 2022

JACC: CardioOncology

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102

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Section: Discussionmentioning

confidence: 92%

Incident Cardiovascular Disease Among Adults With Cancer

Paterson

Wiebe

Cheung

et al. 2022

JACC: CardioOncology

Self Cite

102

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“…Although the gain in running performance was lower in PyMT than in WT mice, it completely counteracted the muscle weakness observed in soleus muscle of PyMT mice. In addition to muscle weakness, cardiovascular disease (CVD) is a common co‐morbidity in patients with cancer, including breast cancer, 36,37 with a 2–6 times higher CVD mortality risk than the general population 36 . Endurance exercise exerts beneficial effects on the whole body and can be used as a powerful tool to enhance cardiac and skeletal muscle function, subsequently reducing the mortality risk and enhancing the quality of life for patients with breast cancer 7 .…”

Section: Discussionmentioning

confidence: 99%

Exercise reduces intramuscular stress and counteracts muscle weakness in mice with breast cancer

Mader

Chaillou

Alves

et al. 2022

J cachexia sarcopenia muscle

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Background Patients with breast cancer exhibit muscle weakness, which is associated with increased mortality risk and reduced quality of life. Muscle weakness is experienced even in the absence of loss of muscle mass in breast cancer patients, indicating intrinsic muscle dysfunction. Physical activity is correlated with reduced cancer mortality and disease recurrence. However, the molecular processes underlying breast cancer‐induced muscle weakness and the beneficial effect of exercise are largely unknown. Methods Eight‐week‐old breast cancer (MMTV‐PyMT, PyMT) and control (WT) mice had access to active or inactive in‐cage voluntary running wheels for 4 weeks. Mice were also subjected to a treadmill test. Muscle force was measured ex vivo. Tumour markers were determined with immunohistochemistry. Mitochondrial biogenesis and function were assessed with transcriptional analyses of PGC‐1α, the electron transport chain (ETC) and antioxidants superoxide dismutase (Sod) and catalase (Cat), combined with activity measurements of SOD, citrate synthase (CS) and β‐hydroxyacyl‐CoA‐dehydrogenase (βHAD). Serum and intramuscular stress levels were evaluated by enzymatic assays, immunoblotting, and transcriptional analyses of, for example, tumour necrosis factor‐α (TNF‐α) and p38 mitogen‐activated protein kinase (MAPK) signalling. Results PyMT mice endured shorter time and distance during the treadmill test (~30%, P < 0.05) and ex vivo force measurements revealed ~25% weaker slow‐twitch soleus muscle (P < 0.001). This was independent of cancer‐induced alteration of muscle size or fibre type. Inflammatory stressors in serum and muscle, including TNF‐α and p38 MAPK, were higher in PyMT than in WT mice (P < 0.05). Cancer‐induced decreases in ETC (P < 0.05, P < 0.01) and antioxidant gene expression were observed (P < 0.05). The exercise intervention counteracted the cancer‐induced muscle weakness and was accompanied by a less aggressive, differentiated tumour phenotype, determined by increased CK8 and reduced CK14 expression (P < 0.05). In PyMT mice, the exercise intervention led to higher CS activity (P = 0.23), enhanced β‐HAD and SOD activities (P < 0.05), and reduced levels of intramuscular stressors together with a normalization of the expression signature of TNFα‐targets and ETC genes (P < 0.05, P < 0.01). At the same time, the exercise‐induced PGC‐1α expression, and CS and β‐HAD activity was blunted in muscle from the PyMT mice as compared with WT mice, indicative that breast cancer interfere with transcriptional programming of mitochondria and that the molecular adaptation to exercise differs between healthy mice and those afflicted by disease. Conclusions Four‐week voluntary wheel running counteracted muscle weakness in PyMT mice which was accompanied by reduced intrinsic stress and improved mitochondrial and antioxidant profiles and activities that aligned with muscles of healthy mice.

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“…Tadic et al's retrospective study using echocardiography examined the strain values in 122 cancer patients before the start of therapy and found a reduction in all three dimensions (16). The probability of systolic impairment is significantly higher in haematooncological diseases (17); however, humoral factors favouring myocardial dysfunction have also been discovered in breast cancer (18). Cancer causes the release of inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

CMR Reveals Myocardial Damage from Cardiotoxic Oncologic Therapies in Breast Cancer Patients

Kersten

Fink

Kersten

et al. 2023

Preprint

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Background Breast cancer is a common and increasingly treatable disease. However, survivors have a significantly elevated risk of cardiac events afterwards. This study aimed to characterise cardiac changes during cardiotoxic cancer therapy using cardiovascular magnetic resonance (CMR) imaging. Methods This study involved 34 patients with histologically proven breast cancer and planned cardiotoxic therapy. All patients underwent CMR before starting therapy, and 6 and 12 months thereafter. The CMR protocol included volumetric and functional analyses, parametric mapping, and deformation analysis using feature tracking. As the control group, 10 healthy female volunteers were scanned using the same protocol. Results With therapy, there was a significant reduction of left ventricular and right ventricular ejection fractions (both p < 0.05). Left ventricular radial (p = 0.008), circumferential (p = 0.010), and longitudinal strain (p = 0.036) were also reduced at follow-up. In the parametric mapping, there was a significant increase in native T1 time (1037 ± 41 ms vs. 1068 ± 51 ms vs. 1017 ± 57 ms, p < .001) and T2 time (55 ± 4 ms vs. 59 ± 3 ms vs. 57 ± 3 ms, p = 0.001), with unchanged extracellular volume and relative late gadolinium enhancement. Twelve months after cancer diagnosis, the breast cancer patients exhibited significant impairments in left ventricular global radial (p = 0.001), circumferential (p = 0.001), and longitudinal strain (p = 0.002) and T2 time (p = 0.008) compared to the healthy controls. Discussion Breast cancer patients receiving cardiotoxic chemotherapy show persistent deterioration in left ventricular strain values. This is accompanied by inflammatory changes in non-invasive tissue characterisation. Larger studies with longer follow-up periods are needed to identify patients at risk and establish preventive and therapeutic approaches.

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Breast cancer diagnosis is associated with relative left ventricular hypertrophy and elevated endothelin-1 signaling

Cited by 12 publications

References 42 publications

Incident Cardiovascular Disease Among Adults With Cancer

Incident Cardiovascular Disease Among Adults With Cancer

Exercise reduces intramuscular stress and counteracts muscle weakness in mice with breast cancer

CMR Reveals Myocardial Damage from Cardiotoxic Oncologic Therapies in Breast Cancer Patients

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