ABSTRACT
Cachexia, a wasting syndrome associated with advanced cancer and metastasis, is rarely documented in breast cancer patients. However, the incidence of cachexia in breast cancer is now thought to be largely underestimated. In our case report of a breast cancer patient with bone metastasis monitored during the course of her treatment, we document the development of cachexia by image analysis in relation to her metastatic burden. Elucidation of the link between metastatic burden and cachexia could unveil a highly specific screening process for metastasis, by assessing true muscle mass loss. Our patient was a 49-year-old premenopausal woman, with metastatic invasive ductal breast carcinoma in the vertebral and iliac bones on presentation, which progressed with new metastases to her hips, thigh bones, and vertebrae. In the two-year period, that is between her diagnosis and death, she lost >10% of her baseline weight. During these two years, we retrospectively identified a decrease in paraspinal muscle (PM) at the third lumbar vertebra followed by a sharp decline in weight. The increased tumor burden over time in metastatic sites was accompanied by a decrease in abdominal muscle and visceral and subcutaneous fat and was followed by the patient’s demise. The increasing tumor burden in the patient was correlated with the mass of other tissues to determine the tissue that could best serve as a surrogate marker to cachexia and tumor burden. We noted a strong negative correlation between PM area and metastatic tumor area at the third lumbar vertebral level, with PM loss correlating to increasing tumor burden. The monitoring of PM wasting may serve as a marker, and therefore a prognostic factor, for both cachexia and extent of metastatic disease, especially in breast cancer, where metastasis to bone is frequent. Based on our data and review of the literature in this case study, longitudinal monitoring of cachexia in the selected muscle groups can give clinicians early indications of the extent of cachexia in metastatic breast cancer patients.
BACKGROUND
Involuntary weight loss seen in several chronic illnesses, such as cancer, is termed cachexia and is distinguished from anorexia by its underlying mechanism. Currently, there is no established consensus for screening patients for cachexia, which can present as fatigue and anorexia, metabolic dysfunction, or systemic inflammation.1 Cachexia is a loss of >5% of body weight primarily due to the loss of muscle mass with or without adipose tissue loss, while anorexia is due to utilization of adipose stores.2 The main underlying pathophysiology of cancer cachexia is thought to be the release of tumor cytokines that interfere with host immunity and cause widespread effects called paraneoplastic syndromes.3–5 Muscle wasting in cachexia may be due to the presence of inflammatory cytokines that cause lipolysis with increased production of brown fat, which causes changes to adipose tissue levels and may present as infiltration of adipose tissue in skeletal muscle, both of which promote increased muscle wasting.4,6 Few options exist for managing symptoms of cachectic patients, beyond increased nutrition and appetite stimulants, none of which have been shown to decrease muscle wasting.7 Not surprisingly, cachexia remains a significant predictor of mortality in cancer patients.
Metastasis is believed to be responsible for ~90% of cancer patient deaths,8,9 and cachexia is found in 50–80% of patients with advanced cancers, largely overlapping with metastatic disease.3,10,11 Metastasis may increase the paraneoplastic potential of cancer, and cachexia may promote further spread of cancer as the body weakens gradually.12 This is illustrated by the observation that cancer cachexia is considered an early complication after diagnosis of gastric or pancreatic cancer, but a late complication following breast or lung cancer diagnosis. Overall, cachexia is associated with the advanced stages of most cancer subtypes.5,7
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Cachexia has been most prevalent in pancreatic, gastric, colorectal, lung, and head and neck cancers13 and is not often documented in breast cancer patients. However, recent studies by Waning and Guise have shown that in breast cancer patients, the relationship between metastasis and cachexia may be more complex than originally thought. In fact, cachexia is largely observed in settings with metastases to bony sites that might directly have an effect on muscle, as part of the body’s normal musculoskeletal endocrine system.4,12 By studying the case of a patient with the rare syndrome of cachexia associated with her metastatic breast cancer, we aimed to define characteristics of the cancer–cachexia relationship. We found that increased metastatic breast cancer tumor burden in our patient correlated strongly with a decrease in muscle mass and excess weight loss.
