Understanding cachexia and muscle dysfunction in the context of metastatic breast cancer

Cancer cachexia significantly impacts the quality of life of cancer patients, predicting therapy response and survival. Cachexia prevalence and severity increases over the course of disease progression, affecting up to 80% of patients with metastatic cancer. Despite this, cachexia is relatively understudied in the context of metastatic breast cancer, despite it affecting a significant proportion of patients with this common cancer. In this review we highlight the relative prevalence of cachexia in breast cancer, with 25% of all patients and up to half of those with metastatic disease impacted. Given the metastatic distribution pattern of breast cancer (e.g. high rates of bone metastases), we reviewed the unique systemic and local muscle cues leading to cachexia in this context and have reviewed areas for further investigation. Furthermore, anti-cancer therapies also contribute to cachexia progression. Recently, novel mouse models for study of cachexia in breast cancer have been developed. These models can further the field's understanding of cachexia in metastatic cancer patients and aid in the development of anti-cachectic agents. However, it is important that these models accurately recapitulate human disease. In this review we provide an appraisal of the relative utility of the currently available models. Overall, this review highlights that understanding cachexia in the context of breast cancer and metastasis may uncover novel mechanisms to target this condition, thereby improving the quality of life and survival prospects of metastatic cancer patients.