Curing breast cancer and killing the heart: A novel model to explain elevated cardiovascular disease and mortality risk among women with early stage breast cancer

Kirkham, Amy A.; Beaudry, Rhys; Paterson, Ian; Mackey, John R.; Haykowsky, Mark J.

doi:10.1016/j.pcad.2019.02.002

Cited by 54 publications

(55 citation statements)

References 115 publications

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“…TNBC is a special subtype of breast cancer, which is aggressive, prone to recurrence and metastasis, and poor in prognosis when compared to other types of breast cancer [24]. Currently, chemotherapy is still the only option for treating TNBC, but treatment outcome is far from satisfying [25]. erefore, novel and e ective therapeutic methods for the treatment of TNBC are urgently needed.…”

Section: Discussionmentioning

confidence: 99%

Engineered IL-7 Receptor Enhances the Therapeutic Effect of AXL-CAR-T Cells on Triple-Negative Breast Cancer

Zhao

Liu

et al. 2020

BioMed Research International

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Triple-negative breast cancer (TNBC) is a very aggressive malignant type of tumor that currently lacks effective targeted therapies. In hematological malignancies, chimeric antigen receptor T (CAR-T) cells have shown very significant antitumor ability; however, in solid tumors, the efficacy is poor. In order to apply CAR-T cells in the treatment of TNBC, in this study, constitutively activated IL-7 receptor (C7R) that has been reported is used to enhance the antitumor function of constructed CAR-T cells by ourselves. Using in vitro coincubation experiments with target cells and in vivo antitumor experiments in mice, we found that the coexpressed C7R can significantly improve the activation, cell proliferation, and cytotoxicity of CAR-T cells. In addition, the in vivo experiments suggested that the enhanced CAR-T cells displayed significant antitumor activity in a TNBC subcutaneous xenograft model, in which in vivo, the survival time of CAR-T cells was prolonged. Together, these results indicated that CAR-T cells that coexpress C7R may be a novel therapeutic strategy for TNBC.

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Section: Discussionmentioning

confidence: 99%

Engineered IL-7 Receptor Enhances the Therapeutic Effect of AXL-CAR-T Cells on Triple-Negative Breast Cancer

Zhao

Liu

et al. 2020

BioMed Research International

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“…Consequently, breast cancer patients, even if they are cured of their cancer, may experience a reduced overall life expectancy due to pre-existing susceptibility to comorbidities and late adverse effects of treatment [61,62]. This may, in particular, play a role for young breast cancer patients, as they tend to present with more aggressive tumor characteristics [63], which requires more comprehensive treatment, putting these women at risk of developing more severe treatment-induced chronic adverse effects [64]. Hence, the potential long period of post-diagnostic survival for most breast cancer patients provides a context in which long-term exposure to an unfavorable lifestyle may have a substantial impact on morbidity and overall mortality.…”

Section: Discussionmentioning

confidence: 99%

Exploring the effects of lifestyle on breast cancer risk, age at diagnosis, and survival: the EBBA-Life study

Lofterød

Frydenberg

Flote

et al. 2020

Breast Cancer Res Treat

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Purpose Whether an unfavorable lifestyle not only affects breast cancer risk, but also influences age at onset of breast cancer and survival, is under debate. Methods In a population-based cohort, the Energy Balance and Breast Cancer Aspects throughout life (EBBA-Life) study, a total of 17,145 women were included. During follow-up, 574 women developed invasive breast cancer. Breast cancer cases were followed for an additional 9.1 years. Detailed medical records were obtained. Cox's proportional hazard regression models were used to study the association between pre-diagnostic lifestyle factors (weight, physical activity, alcohol use, smoking, and hypertension), breast cancer risk, age at diagnosis, and survival. Results At study entry, 34.3% of the participating women were overweight and 30.7% were physically inactive. Mean age at breast cancer diagnosis was 58.0 years, and 78.9% of the tumors were estrogen receptor positive. Among menopausal women who did not use hormone therapy and had an unfavorable lifestyle (3-5 unfavorable factors), compared with women who had a favorable lifestyle, we observed a twofold higher risk for postmenopausal breast cancer (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.23-3.69), and they were 3.4 years younger at diagnosis (64.8 versus 68.2 years, P = 0.032). Breast cancer patients with an unfavorable lifestyle, compared with patients with a favorable lifestyle, had almost a two times higher overall mortality risk (HR 1.96, 95% CI 1.01-3.80). Conclusions Our study supports a healthy lifestyle improving breast cancer prevention, postponing onset of disease, and extending life expectancy among breast cancer patients.

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“…The adverse changes in skeletal muscle quality, mass, and oxidative capacity contribute to a range of functional consequences and negative outcomes, including decreased quality of life (QOL) [ 57 ], fatigue [ 58 ], arm lymphedema [ 59 ], muscle weakness [ 29 ], diminished capacity to perform activities of daily living [ 60 ], and poor prognosis [ 61 ]. Impairment in skeletal muscle structure and function have also been linked to reduced VO 2peak and exercise intolerance [ 23 ], which may be the limitation of skeletal muscle dysfunction most tightly associated with whole-body health and CVD risk [ 31 ]. Dysfunctional components of the cardiovascular-muscular axis may partially mediate the association between VO 2peak and CVD risk.…”

Section: Cardiovascular and Clinical Repercussions Of Skeletal Musmentioning

confidence: 99%

“…As such, exercise intolerance may contribute to CVD risk in breast cancer survivors by limiting the potential to garner cardioprotective benefits from exercise. Ultimately, limitations at the level of the skeletal muscle may hamper breast cancer survivors’ ability to (i) engage in consistent aerobic exercise training, and/or (ii) reach a high enough exercise intensity to reap cardioprotective effects [ 31 ].…”

Section: Cardiovascular and Clinical Repercussions Of Skeletal Musmentioning

confidence: 99%

“…While skeletal muscle dysfunction may be preexisting, it can also be a direct (e.g., anthracycline-mediated skeletal muscle damage) or indirect (e.g., atrophy as a result of treatment-mediated physical inactivity) consequence of traditional treatments [ 12 , 19 , 28 , 29 , 30 ]. Skeletal muscle dysfunction may be a central component linking many therapy-related toxicities and lifestyle factors with overall CVD risk, and is potentially a unique, additional contributor to CVD risk in this population [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

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Cardiovascular Consequences of Skeletal Muscle Impairments in Breast Cancer

Zieff

Wagoner

Paterson

et al. 2020

Sports

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Breast cancer survivors suffer from disproportionate cardiovascular disease risk compared to age-matched controls. Beyond direct cardiotoxic effects due to treatments such as chemotherapy and radiation, breast-cancer-related reductions in skeletal muscle mass, quality and oxidative capacity may further contribute to cardiovascular disease risk in this population by limiting the ability to engage in aerobic exercise—a known promoter of cardiovascular health. Indeed, 20–30% decreases in peak oxygen consumption are commonly observed in breast cancer survivors, which are indicative of exercise intolerance. Thus, breast-cancer-related skeletal muscle damage may reduce exercise-based opportunities for cardiovascular disease risk reduction. Resistance training is a potential strategy to improve skeletal muscle health in this population, which in turn may enhance the capacity to engage in aerobic exercise and reduce cardiovascular disease risk.

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Curing breast cancer and killing the heart: A novel model to explain elevated cardiovascular disease and mortality risk among women with early stage breast cancer

Cited by 54 publications

References 115 publications

Engineered IL-7 Receptor Enhances the Therapeutic Effect of AXL-CAR-T Cells on Triple-Negative Breast Cancer

Engineered IL-7 Receptor Enhances the Therapeutic Effect of AXL-CAR-T Cells on Triple-Negative Breast Cancer

Exploring the effects of lifestyle on breast cancer risk, age at diagnosis, and survival: the EBBA-Life study

Cardiovascular Consequences of Skeletal Muscle Impairments in Breast Cancer

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