Determinants of exercise intolerance in breast cancer patients prior to anthracycline chemotherapy

Abstract

Women with early‐stage breast cancer have reduced peak exercise oxygen uptake (peak VO2). The purpose of this study was to evaluate peak VO2 and right (RV) and left (LV) ventricular function prior to adjuvant chemotherapy. Twenty‐nine early‐stage breast cancer patients (mean age: 48 years) and 10 age‐matched healthy women were studied. Participants performed an upright cycle exercise test with expired gas analysis to measure peak VO2. RV and LV volumes and function were measured at rest, submaximal and peak supine cycle exercise using cardiac magnetic resonance imaging. Peak VO2 was significantly lower in breast cancer patients versus controls (1.7 ± 0.4 vs. 2.3 ± 0.5 L/min, P = 0.0013; 25 ± 6 vs. 35 ± 6 mL/kg/min, P = 0.00009). No significant difference was found between groups for peak upright exercise heart rate (174 ± 13 vs. 169 ± 16 bpm, P = 0.39). Rest, submaximal and peak exercise RV and LV end‐diastolic and end‐systolic volume index, stroke index, and cardiac index were significantly lower in breast cancer patients versus controls (P < 0.05 for all). No significant difference was found between groups for rest and exercise RV and LV ejection fraction. Despite preserved RV and LV ejection fraction, the decreased peak VO2 in early‐stage breast cancer patients prior to adjuvant chemotherapy is due in part to decreased peak cardiac index secondary to reductions in RV and LV end‐diastolic volumes.

Exercise Intolerance in Anthracycline-Treated Breast Cancer Survivors: The Role of Skeletal Muscle Bioenergetics, Oxygenation, and Composition

“…Peak VO 2 is a strong independent predictor of CVD, disability, and mortality in healthy and clinical populations [26]. Following BC treatment, women have a peak VO 2 that is on average 20% lower than age-matched healthy sedentary women [3][4][5][6][7][8]. The mechanisms responsible for the reduced exercise tolerance are not well understood; however, recent evidence suggests that "noncardiac" peripheral abnormalities associated with chemotherapy may be important contributors to reduced exercise tolerance [13,16].…”

“…Women with a history of BC are at greater risk for CVD and related mortality relative to women without BC. It is well established that following treatment for BC, cardiorespiratory fitness, measured as peak oxygen uptake (peak VO 2 ) during whole-body exercise, is ≈20% lower than age-and sex-matched controls [3][4][5][6][7][8]. Low cardiorespiratory fitness is associated with increased heart failure incidence, cardiovascular events, and both CVDrelated and all-cause mortality [9].…”

Cardiovascular Consequences of Skeletal Muscle Impairments in Breast Cancer

“…The deleterious effects of breast cancer-related treatment and lifestyle factors can negatively affect skeletal muscle size, which can contribute to functional limitations, including exercise intolerance [ 12 , 23 , 28 ]. Decreased muscle size, fiber cross-sectional area, and myocyte size have been reported in a number of cancers, including breast cancer [ 12 , 39 , 40 ].…”

“…Though these treatments are not used solely in breast cancer and thus elicit cardiotoxic effects in other cancer populations [ 17 ], these effects may be particularly harmful in breast cancer survivors since (i) CVDs and breast cancer share risk factors (e.g., hypercholesteremia, hypertension, obesity) [ 18 , 19 , 20 ] and (ii) most women are diagnosed with breast cancer after menopause, a period when CVD risk increases due to declining estrogen [ 21 , 22 ]. Additionally, many lifestyle factors such as physical inactivity and obesity (which may exist at the time of diagnosis, or develop/worsen following diagnosis and treatment) influence these shared risk factors, and may exacerbate cardiotoxic effects of treatments, thereby further contributing to CVD risk [ 23 , 24 , 25 ]. Interestingly, skeletal muscle dysfunction—including reductions in mass, quality, and oxidative capacity—is also a side-effect of cancer treatment, and has been observed in various cancer types [ 26 , 27 ], including breast cancer [ 12 , 28 ].…”

“…The detrimental effects of breast cancer treatment and lifestyle factors on cardiovascular health have been evaluated using gold standard cardiopulmonary exercise testing (CPET) assessment of peak oxygen consumption (VO 2peak ) [ 23 , 33 , 34 ]. VO 2peak is a global indicator of the function of the cardiovascular-muscular axis which facilitates the intake, transport, uptake, and utilization of oxygen, and is related to the capacity to perform aerobic exercise.…”