Physical activity and cancer

Physical activity and primary prevention of malignant diseases

Based on the close relationship between PA, bodyweight and all-cause mortality, one can wonder whether the risk of affection of a malignant disease also depends on body weight or, respectively, PA. As shown in a meta-analysis of 282, 317 cancer cases, increased body mass index (BMI) is associated with an increased risk of cancer. For example, compared with people of normal body weight, there is a 1.5-fold increase in risk for oesophagus-carcinoma with every 5 kg/m²-increment of BMI^[11].

A weak point of many studies concerning the issue ‘PA and cancer’ is due to methodical reasons – it may be difficult to acquire PA in proper style during everyday life^[12]. However, there is epidemiological evidence that cancer-protective effects of PA are rather under, than overestimated by common methods of acquisition of PA (questionnaire, accelerometer)^[13].

An inverse association between PA and cancer incidence was found in a large cohort study of 40,700 men^[14]. Currently, largest evidence for primary-preventive effects of PA on cancer risk can be found for colon carcinoma^[15]. In summary, between 9% and 19% of the most common tumours seems to be attributed to deficit PA^[16]. As especially the risk for the most common tumours (e.g. cancer of breast and colon) seems to be reduced, increase in PA in terms of behaviour-oriented prevention offers an enormous potential for general population health care.

Compared with cardiovascular diseases^[17], there is equivocality concerning the mechanisms of primary-preventive effects of PA on risk of cancer. On the one hand, this may be due to the fact that ‘cancer’ summarises many heterogeneous diseases of different aetiology, and on the other hand, ‘PA’ is also only a superordinate concept of a complex behaviour which elicits various physical and psychic reactions of the organism. As a multiplicity of biological modes of action can be taken into account, an entity-specific approach is needed. Generally^{[18,19,20,21]}, increase in muscle mass and, accordingly, reduction in body fat as a consequence of PA result in positive endocrinological alterations (sex/ steroid hormones, growth factors, insulin/insulin resistance) which finally inhibit carcinogenesis. Positive influence of PA on ‘oxidative stress’, inflammation and DNA repair mechanisms as well as its induction of specific gene expression patterns and, respectively, extensive effects of PA on the immune system are discussed as further possible unspecific mechanisms (Figure 1). Accelerated gastro-intestinal transition time and – as a consequence – reduced contact time of carcinogen substances with the mucosa also seems to be responsible that of all things, primary-preventive effects of PA on risk of colon carcinoma are especially high^[22].

Figure 1: Potential mechanisms of primary-preventive effects of physical activity on risk of cancer.

Physical activity as cancer-support therapy

As a residue of former therapeutic standards, the thought that cancer patients should rest and do not bear or are even marred by PA still haunts some people’s mind^[23]. Typical consequence of cancer disease and therapy such as surgery-induced limitation of flexibility or even immobility, side-effects of drugs (anaemia, cardiotoxicity, pulmonary toxicity), sarcopaenia, myopathy, susceptibility to infection, pain, anxiety, mental stress, depression, insomnia, nutritional disturbance (malnutrition, cachexia) may result in breathlessness, tachycardia and fatigue^[24]. Therefore, at first glance it may be traceable that PA in terms of a cancer-support therapy is considered to be an unreasonable demand for cancer patients. However, physical protection/inactivity may end up in a vicious circle (Figure 2): muscle mass is reduced as well as cardiac and, respectively, pulmonary exercise capacity and – as consequence – endurance capacity and muscular strength. Former activities of daily living are getting more and more difficult for the patients and are thus avoided whereupon inactivity and physical protection are further increased.

Figure 2: Vicious circle of physical protection and inactivity.

Thus, breakthrough of this vicious circle is an important aim of PA within the scope of tumour therapy. For that matter, numerous studies showed that PA during tumour therapy results in a reduction in fatigue^[24,25], an increase in quality of life and exercise capacity^[26] and a reduction in treatment-associated disorders such as nausea, fatigue, insomnia and pain^[27]. Therefore, PA during ongoing cancer treatment is considered to be an effective cancer-support therapy without any negative effects if relevant contraindications are considered. Contraindications for participation are similar to those of healthy people and, respectively, patients with chronic diseases^[28]. Specific characteristics of cancer- or therapy-related alterations of the patient have to be considered. Table 1 gives an overview of general contraindications of sport participation, whereupon attention of the specific situation of a patient is always a necessity^[28,29].

Table 1 Contraindications of sport participation of cancer patients

Preliminary assessment of cancer patients includes clinical status, laboratory parameters and exclusion of skeletal instability. Cardiological examination is essential for older patients, patients at risk for coronary heart disease and after high-dose chemotherapy or treatment with cytostatic drugs with cardiotoxicity or pulmonary toxicity. Examination should include resting- and stress-ECG, echocardiography and pulmonary function test for assessment of exercise capacity, additional (e.g. invasive) diagnostics may be necessary in certain clinical situations^[28,30].

Training programme^{[29,30,31,32,33,34,35]} should respect the patient’s affinity for certain sports. Very often, cancer patients exhibit a severely reduced exercise capacity. Therefore, a frequent and individual monitoring is important. A combination of resistance and endurance training, for example, jogging, walking, bicycling, gymnastics or (under consideration of general state of health and immune state) rowing and swimming is recommended for cancer patients. Ball games or contact sports may be dangerous for patients with impaired blood coagulation. Endurance training (30–45 min/day) should be performed with 70%–80% of maximal exercise capacity, a modulation of intensity due to concomitant disease (coronary heart disease, arterial occlusive disease, diabetes, osteoarthritis) may be needed but with possibly consecutive reduction in effectiveness of training. Reduction in intensity due to a generally reduced state of health of the patient to offer sports participation results in a disproportional increase in training time and is therefore not generally recommended. However, training with reduced intensity may be focused on muscle coordination to improve motor deficits in some of these patients. If hygiene factors for immunosuppressed patients are considered, sports participation is also possible for patients with leukopaenia/neutropaenia.

Physical activity in follow-up care

Negative influence of overweight/obesity and, respectively, positive effects of PA concerning risk of cancer disease have been already discussed. Hence, the question comes up whether factors such as bodyweight and PA are able to modulate prognosis of malign diseases. The correlation between BMI at baseline and risk of cancer-related death during follow-up was examined in a large cohort study with 900,000 subjects who did not have cancer diagnosis at baseline^[36]. During follow-up (16 years), there was a 52% (♂) and accordingly 62% (♀) increase in risk of cancer-related death of the most obese (BMI > 40 kg/m²) compared with subjects with normal body weight. An association between BMI and increased mortality was also found for cancer of the colon and rectum, oesophagus, liver, gallbladder, pancreas and kidney and for death due to non-Hodgkin’s lymphoma and multiple myeloma. Significant trends were observed for death from stomach cancer and prostate in men and for death from breast, uterus, cervix and ovary cancers in women. Based on these associations, it was calculated that overweight and obesity in the United States could account for 14%–20% of all deaths from cancer.

Concerning positive effects of PA on prognosis, there is good evidence for colon carcinoma. For example, in a prospective study by Meyerhardt et al.^[37] with 573 patients suffering from colon carcinoma (I–III), dependency of cancer-related and accordingly all-cause mortality on PA before and after diagnosis and, respectively, changing of PA after diagnosis was examined. Cancer-related and all-cause mortality was not influenced by degree of PA before diagnosis but was modulated – the more, the better – by magnitude of PA after diagnosis, whereupon it did not play a role whether the patients were physically active at a defined level already before or as recently as after diagnosis. Similar results became apparent at patients with breast cancer wherein exact entity (e.g. receptors) plays an important role^[38]. At other cancer entities, there is no or at most minor evidence for a prognosis-modulation effect of PA^[39].

However, due to its multi-dimensional effects, PA plays an important role in follow-up care of cancer patients even independent of the influence on prognosis. PA is effective concerning improvement of exercise capacity, acts as antidepressant and enhances mental health and body functioning^[40]. At the moment, there is no acceptably data if these effects can be observed also in a palliative situation^[41]. Finally, PA promotes social re-integration and results in a better quality of life^[12,42].