Early skeletal muscle deconditioning and reduced exercise capacity during (neo)adjuvant chemotherapy in patients with breast cancer

Abstract

Background Fatigue is a hallmark of breast cancer and is associated with skeletal muscle deconditioning. If cancer‐related fatigue occurs early during chemotherapy (CT), the development of skeletal muscle deconditioning and its effect on exercise capacity remain unclear. The aim of this study was to investigate the evolution of skeletal muscle deconditioning and exercise capacity in patients with early‐stage breast cancer during CT. Methods Patients with breast cancer had a visit before undergoing CT, at 8 weeks, and at the end of chemotherapy (post‐CT). Body composition was determined through bioelectrical impedance analysis. Knee extensor, handgrip muscle force and fatigue was quantified by performing maximal voluntary isometric contractions and exercise capacity using the 6‐min walking test. Questionnaires were also administered to evaluate quality of life, cancer‐related fatigue, and physical activity level. Results Among the 100 patients, reductions were found in muscle mass (−2.3%, p = .002), exercise capacity (−6.7%, p < .001), and knee extensor force (−4.9%, p < .001) post‐CT, which occurred within the first 8 weeks of treatment with no further decrease thereafter. If muscle fatigue did not change, handgrip muscle force decreased post‐CT only (−2.5%, p = .001), and exercise capacity continued to decrease between 8 weeks and post‐CT (−4.6%, p < .001). Quality of life and cancer‐related fatigue were impaired after 8 weeks (p < .001) and remained stable thereafter, whereas the physical activity level remained stable during chemotherapy. Conclusions Similar to cancer‐related fatigue, skeletal muscle deconditioning and reduced exercise capacity occurred early during breast cancer CT. Thus, it appears essential to prevent these alterations through exercise training implemented during CT.

A single chemotherapy administration induces muscle atrophy, mitochondrial alterations and apoptosis in breast cancer patients

“…On the other hand, it should be noted that PGC‐1α1 is also implicated in several other cellular processes, such as thermogenesis, glucose uptake or lipogenesis, 18 which could also explain its increase post‐EC. Overall, as mitochondrial content and function are directly related to exercise capacity, 19 our results may explain the early decrease in exercise capacity observed in breast cancer patients treated with chemotherapy 20 …”

“…Overall, as mitochondrial content and function are directly related to exercise capacity, 19 our results may explain the early decrease in exercise capacity observed in breast cancer patients treated with chemotherapy. 20 A decrease in mitochondrial content has been previously associated with impairment of mitochondrial dynamics in breast cancer patients 14 characterized by an imbalance between fusion and fission processes. In this study, if the markers of mitochondrial fission (Fis1 and DRP1) were not altered post-EC or post-TAX, a decrease in the protein level of OPA1, a key marker of mitochondrial inner-membrane fusion, was observed only from pre-to post-EC.…”

“…The alterations observed in the present study post-EC, may explain, at least in part, the early decrease in muscle force and exercise capacity observed in breast cancer patients. 20 Indeed, muscle mass is strongly correlated to the force production 36 and mitochondrial content and function are directly related to the exercise capacity. 19 We previously reported in a cohort of 100 patients with breast cancer that knee extensors muscle force and exercise capacity were reduced at 8 weeks of treatment (i.e., after two or three EC administrations).…”

“…19 We previously reported in a cohort of 100 patients with breast cancer that knee extensors muscle force and exercise capacity were reduced at 8 weeks of treatment (i.e., after two or three EC administrations). 20 However, exercise capacity further decreased between 8 weeks and the end of chemotherapy treatment. 20 Thus, other mechanisms may be involved in this decrease, such as the well-accepted neurotoxicity induced by TAX administration 37 or the cardiotoxicity induced by EC administration.…”

“…20 However, exercise capacity further decreased between 8 weeks and the end of chemotherapy treatment. 20 Thus, other mechanisms may be involved in this decrease, such as the well-accepted neurotoxicity induced by TAX administration 37 or the cardiotoxicity induced by EC administration. 38 We also recently demonstrated that the reduction in exercise capacity was associated with exacerbated central fatigue during exercise in patients compared with their healthy counterparts.…”