Interesting. I just helped a friend (a top level triathlete) who did her Masters thesis on Exercise and Cancer Patients, both during and post surgery/chemotherapy. It sounds worse than it is. Tasha, (Gazelle) who posts here can provide real world experience.
Several of the aforementioned side effects of chemotherapy and radiation affect the hematopoietic, pulmonary and cardiovascular systems. All of these systems are integral to generating the physiological response required to meet the increased demand for oxygen during exercise. There are three side effects in particular, that have a high potential to alter exercise physiology in a breast cancer patient or survivor. These side effects, decreased red blood cell (RBC) production, cardiotoxicity and pulmonary toxicity, will be the focus of discussion due to their combined high prevalence and dramatic effect on the response to exercise.
Chemotherapy and radiation can destroy cells in the bone marrow, decreasing its ability to replace used blood cell elements, such as RBCs {{82 Wilkes, G.M. 1996; }}. Decreased RBC production can lead to anemia, which occurs in 30-90% of patients with cancer {{42 Knight,Kevin 2004; }}. Although there are interventions available to treat anemia, such as transfusions and erythropoietin stimulators, very few breast cancer patients actually receive treatment during adjuvant chemotherapy {{199 Goldrick, A. 2007; }}. During exercise in otherwise healthy people, anemia is associated with a reduction of maximal oxygen consumption (VO2max), an indication of aerobic fitness, and both maximal {{44 Zarychanski, R. 2008; }} and submaximal performance {{43 Sorace, P. 2007}}. The reduced oxygen content of the blood with anemia causes cardiac output and muscle blood flow to increase at a greater rate during exercise, and remain higher relative to the intensity of exercise through the workout {{43 Sorace, P. 2007}}. Due to the alterations in cardiac output, heart rate will increase quicker and remain higher throughout the workout.
Some chemotherapy drugs used to treat breast cancer can cause permanent or transient adverse effects to the myocardium, known as cardiotoxicity. Cardiomyocytes are thought to be damaged by free radical generation leading to oxidative stress {{22 Bird, B.R.J.H. 2008}}. Intracellular calcium influx and overload are also linked with cardiomyocyte membrane damage and cell death, respectively {{374 Shan,Kesavan 1996; }}. Radiation treatment for breast cancer is also associated with cardiotoxicity, and has the potential to affect all structural components of the heart, rather than just the myocardium, as is common with chemotherapy {{58 Berry,Gerald J. 2005; }}. The specific mechanism of Trastuzumab-induced cardiotoxicity is not clearly defined, but there is an increased incidence when used in combination with chemotherapy {{198 Perik,Patrick J. 2007; }}. Cardiotoxicity may present as a variety of clinical manifestations. Some examples include tachycardia, bradycardia, other arrhythmias, decreased left ventricular ejection fraction (LVEF), diastolic dysfunction, pericarditis, myocarditis, cardiomyopathy, myocardial ischemia, myocardial infarction, and heart failure {{23 Floyd, J.D. 2005; 50 Dempsey, K.S. 2008; 22 Bird, B.R.J.H. 2008}}. Many of the effects of cardiotoxicity are asymptomatic or silent, which often leaves structural changes that may affect cardiac function and performance during exercise undetected. The predominant indicator of cardiotoxicity is decreased contractility of the left ventricle {{84 Ewer,Michael S. 2008; }}. The criterion used to indicate cancer treatment-induced decreased cardiac contractility is a decreased left ventricular ejection fraction (LVEF), however this measurement, calculated by the stroke volume divided by end diastolic volume, is known to lack sensitivity in detecting cardiomyocyte damage {{84 Ewer,Michael S. 2008; }}. Chemotherapy drugs used to treat breast cancer are some of the most cardiotoxic drugs {{50 Dempsey, K.S. 2008}}, yet, the actual prevalence is likely greatly underestimated by this insensitive measurement technique {{84 Ewer,Michael S. 2008; }}. Most reported prevalence rates cite only severe cases of cardiotoxicity (i.e. heart failure), while the extent of damage that is required to affect the cardiac response to exercise is considerably less. Modern radiation techniques limit the exposure of the heart to the radiation beams, and follow-up with patients who have received this treatment have not shown an increased risk of cardiac disease {{57 Shapiro,Charles L. 2001; }}. However, there is a trend toward higher incidence of cardiac perfusion defects (an indication of heart disease) with increasing volume of left ventricle exposed to radiation {{179 Marks,Lawrence B. 2005; }}. Some of these manifestations of cardiotoxicity discussed would be contraindications to exercise, but for the less severe conditions, and for any damage preceding the conditions, there are changes in the cardiac response to exercise that can be predicted. For example, with decreased myocardial contractility, preload is much less effective in increasing stroke volume; and with arrhythmias, such as bradycardia or tachycardia the relationship between heart rate and oxygen consumption, and thus exercise intensity would be altered.
Pulmonary toxicity can occur through direct or indirect (via a signal transduction pathway) damage leading to cell apoptosis, and a loss of integrity in pulmonary capillaries, leading to loss of lung compliance, decreased gas exchange, and even respiratory failure {{53 Abid,Syed H. 2001; }}. Pulmonary toxicity is much easier to detect than cardiotoxicity. An insidious onset of dyspnea associated with a nonproductive cough is the typical symptom associated with chemotherapy-induced pulmonary toxicity, and can aid in early diagnosis {{53 Abid,Syed H. 2001}}. There is also a test for pulmonary toxicity with enough sensitivity to detect abnormalities prior to symptoms {{55 Camp-Sorrell, D. 2005/s446;}}. The literature shows that pulmonary toxicity is more common in chemotherapy drugs used to treat non-breast cancers, with documented incidence rates of up to 40% {{53 Abid,Syed H. 2001}}. Prevalence has not been assessed for most of the current adjuvant chemotherapy protocols commonly used for breast cancer {{164 Yerushalmi, R. 2009; }}. However, one recent study that specifically investigated pulmonary function following breast cancer chemotherapy, showed a decline in carbon monoxide diffusion capacity, adjusted for hemoglobin levels, in all 34 subjects, while only five reported dyspnea {{164 Yerushalmi, R. 2009; }}. This study suggests that like cardiotoxicity, the prevalence of pulmonary toxicity in breast cancer treatment may be underestimated. Pneumonitis is the clinical syndrome associated with radiation-induced pulmonary toxicity. It is fairly rare, occurring in less than 1% of women treated with radiation alone, with a higher incidence when chemotherapy is given concurrently {{57 Shapiro,Charles L. 2001; }}. Chemotherapy-induced damage to the lungs may ultimately result in restrictive lung disease, decreased lung volume, increased work of breathing and impaired gas exchange {{55 Camp-Sorrell, D. 2005/s446;}}. Hypoxemia will occur as a result of impaired oxygen diffusion coupled with uninterrupted perfusion to damaged areas of the lung {{55 Camp-Sorrell, D. 2005/s446;}}. This low oxygen concentration in the blood results in impaired oxygen delivery to the muscles, especially during exercise.
In summary, chemotherapy and radiation treatment for breast cancer can result in several mechanisms of damage resulting in side effects that alter the hematopoietic, cardiovascular and pulmonary systems. With the knowledge of anemia’s effects in otherwise healthy individuals, the effect of myocardial damage on heart contractility and the effect of impaired gas exchange at the alveoli, an idea of the repercussions of chemotherapy and radiation treatment on the cardiovascular exercise response can be inferred. Specifically, these side effects cause a change in stroke volume, due to decreased myocardial contractility; as well as impaired oxygen delivery, due to impaired oxygen carrying capacity of the blood and impaired gas exchange. At rest and light activity, the cardiovascular system can typically compensate for these impairments in oxygen delivery to tissues through an increase in heart rate to compensate for the decreased stroke volume. Note that cardiac output is calculated as the product of heart rate and stroke volume. However, when exercise is performed, the ability to compensate is not enough to fulfill oxygen requirements of the metabolically active muscles. During exercise in a healthy individual, blood flow is shunted from the less active tissues, via vasoconstriction in viscera arterioles, toward the respiratory muscles and skeletal muscles being used, via vasodilation in skeletal muscle arterioles, enhancing oxygen delivery to these tissues. As the exercise intensity increases, the amount of oxygen consumed and delivered to the exercising muscles increases concurrently {{187 Anonymous 2005/s340;}}. The increased demand for oxygen is met by increased responses in cardiac output and pulmonary oxygen diffusion capacity. Individuals treated for breast cancer may experience decreased responses in these parameters, and the decreased oxygen carrying capacity of the blood, as experienced by most cancer patients, will compound this effect. So for these individuals, an altered response to exercise would occur: delivery is not effectively increased to meet the increased requirement for oxygen, thereby negatively affecting exercise capacity.
With an idea of the specific cardiovascular ramifications of chemotherapy and radiation treatment side effects, an effect on exercise prescription can then be inferred. There are three determinants of oxygen consumption by tissue. The Fick equation states that maximal oxygen consumption (VO2max), the maximum capacity of an individual's body to transport and utilize oxygen during exercise, is equal to the product of cardiac output and arteriovenous oxygen content difference. According to the Fick equation, the first determinant is the rate at which oxygen is transported to the tissues. Blood flow increases very quickly in response to increased heart rate, which increases oxygen transport during exercise. In addition to alterations in the vascular system to redirect blood flow, an increase in blood flow is mediated by an increased cardiac output. However, the decreased cardiac output that would occur when stroke volume is diminished by cardiotoxicity, combined with a diminished ability to increase stroke volume in response to exercise, would limit the increase in blood flow in affected individuals. The second determinant is the oxygen-carrying capacity of the blood. This determinant is directly affected by anemia, which occurs in up to 90% of cancer patients. The last determinant of oxygen consumption is the amount of oxygen extracted from the blood. Although the arteriovenous oxygen content difference, a measurement of this determinant, can be affected in cancerous cells when compared to normal tissue, it is unknown whether any change occurs in a cancer patient’s skeletal muscle {{182 Beaney,RonaldP. 1984; }}. Maximal oxygen consumption is likely to be negatively affected by these alterations of the determinants of oxygen consumption. The individual’s heart rate response to exercise would also be moderated. Specifically, heart rate would be higher for any given submaximal exercise intensity or workload due to the need for compensation for cardiac output. As will be discussed later, exercise prescription, specifically exercise intensity prescription, is based on the metabolic and/ or heart rate response to exercise.
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