Clinical implications of low skeletal muscle mass in early-stage breast and colorectal cancer

Abstract

Although obesity has now been widely accepted to be an important risk factor for cancer survival, the associations between body mass index and cancer mortality have not been consistently linear. Although morbid obesity has clearly been associated with worse survival, some studies have suggested a U-shaped association with no adverse association with overweight or lower levels of obesity. This “obesity paradox” may be due to the fact that body mass index likely incompletely captures key measures of body composition, including distribution of skeletal muscle and adipose tissue. Fat and lean body mass can be measured using clinically acquired CT scans. Many of the earlier studies focused on patients with metastatic cancer. However, skeletal muscle loss in the metastatic setting may reflect end stage disease processes. Therefore, this article focuses on the clinical implication of low skeletal muscle mass in early stage non-metastatic breast and colorectal cancer where measures of body composition have been shown to be strong predictors of disease-free survival and overall survival and also chemotherapy toxicity and operative risk.

Systemic Actions of Breast Cancer Facilitate Functional Limitations

“…This observation is consistent with a higher risk of dying due to low levels of muscle mass in women with breast cancer compared to women who have adequate muscle mass [24]. Furthermore, women with higher muscle mass demonstrate improved response to cancer treatment and overall survival [25,26]. Preclinical data from animal models of breast cancer demonstrated that mice with primary mammary tumors have reduced grip strength and declined motor activity [13].…”

“…However, considering one in eight women in the United States is diagnosed with breast cancer and 25% of breast cancer patients, particularly those with triple-negative breast cancer, experience cachexia [2,174], additional studies are needed. Furthermore, myopenic obesity, which not only provides a misguided outlook but also impacts chemotherapy tolerability [26,175], is common in breast cancer patients. Lean muscle mass instead of BMI may need to be measured in breast cancer patients to ensure that there is no muscle loss.…”

Hypoalbuminemia Reflects Nutritional Risk, Body Composition and Systemic Inflammation and Is Independently Associated with Survival in Patients with Colorectal Cancer

“…Furthermore, little is known about whether hypoalbuminemia is associated with survival independent of these parameters. Through the use of Computerized tomography (CT scans), body composition can now be assessed as part of the routine clinical work up of patients with cancer, in particular in patients with operable disease [11]. The aim of the present study was to examine the relationship between hypoalbuminemia, nutrition-related risk, body composition, systemic inflammation and mortality in patients with operable colorectal cancer.…”

Impact of a ketogenic diet intervention during radiotherapy on body composition: III—final results of the KETOCOMP study for breast cancer patients

“…As a result, there is burgeoning interest in researching modifiable factors that causally impact the treatment outcome and prognosis of breast cancer patients. Besides well-known prognostic factors such as age, stage of disease, HER2-Neu expression, and estrogen and progesterone receptor status, factors relating to the cancer patient’s metabolism such as obesity [ 3 , 4 ], sarcopenia [ 5 , 6 ], insulin levels [ 7 , 8 ], and chronic hyperglycemia [ 9 – 11 ] have been shown to possess a prognostic role. Evidence for a causal influence of these metabolic factors comes from preclinical data showing that breast cancer cells are stimulated by insulin [ 12 ] and certain adipokines [ 13 ] and are vulnerable to glucose restriction [ 14 , 15 ].…”

“…Evidence for a causal influence of these metabolic factors comes from preclinical data showing that breast cancer cells are stimulated by insulin [ 12 ] and certain adipokines [ 13 ] and are vulnerable to glucose restriction [ 14 , 15 ]. Unfortunately, a large proportion of newly diagnosed breast cancer patients exhibit high fasting blood glucose levels [ 16 ], obesity, and low muscle mass [ 5 , 6 ]. These phenomena may be exacerbated during radio- and chemotherapy, worsening the health and fitness of patients.…”