Abstract
Breast cancer is a disease of a specific organ, but its effects are felt throughout the body. The systemic effects of breast cancer can lead to functional limitations in patients who suffer from muscle weakness, fatigue, pain, fibromyalgia, or many other dysfunctions, which hasten cancer-associated death. Mechanistic studies have identified quite a few molecular defects in skeletal muscles that are associated with functional limitations in breast cancer. These include circulating cytokines such as TNF-α, IL-1, IL-6, and TGF-β altering the levels or function of myogenic molecules including PAX7, MyoD, and microRNAs through transcriptional regulators such as NF-κB, STAT3, and SMADs. Molecular defects in breast cancer may also include reduced muscle mitochondrial content and increased extracellular matrix deposition leading to energy imbalance and skeletal muscle fibrosis. This review highlights recent evidence that breast cancer-associated molecular defects mechanistically contribute to functional limitations and further provides insights into therapeutic interventions in managing functional limitations, which in turn may help to improve quality of life in breast cancer patients.
Highlights
Cancer-specific genomic aberrations may determine the type of cytokines/chemokines produced by cancer cells and pathways affected in the skeletal muscles
We reported that circulating levels of cardiac and skeletal muscle-enriched miR-486 were lower in breast cancer patients with metastasis compared to healthy individuals [38]
The limited progress is mainly due to the perception that breast cancer patients, compared to other cancer patients, rarely experience cachexia
Summary
40% breast cancer patients demonstrated at least one of the functional limitations [5]. The prevalence of functional limitations in breast cancer patients is dependent on disease stage, age, ethnicity, demographics, and physical compositions [5]. Functional limitations are more common among older breast cancer patients [5,11]. Women with functional limitations are more likely to be overweight or obese with less physically activity [5,12]. Preclinical and clinical data demonstrate that functional limitations result in significantly shorter survival due to non-cancer causes of death [5,13]. 2. Functional Limitation is Likely Due to Skeletal Muscle Dysfunction in Breast Cancer. Growing evidence points to skeletal muscle dysfunction as a major cause of cancer-associated
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