Breast cancer, as the most common kind of cancer, affects 1.1 million women all over the world, and about 58,000 new cases are diagnosed in Germany every year [1, 2]. Breast operation and postoperative chemotherapy/radiotherapy, as a regular treatment, has negative physiological and psychological effects on the patients; these side effects, however, could be counterbalanced by an increased level of physical fitness [3, 4]. Traditionally, clinicians advised cancer patients to rest and to avoid physical activity. During the last two decades, however, exercise training has been recognized as a significant means in the prevention and rehabilitation of breast cancer patients.

Exercise and breast cancer prevention

Several epidemiological studies have shown an inverse relationship between the risk of breast cancer and physical activity levels [5–9]. McTiernan et al. [5] prospectively examined the association between current and past recreational physical activity and incidence of breast cancer in postmenopausal women (n = 75,171). Women who have been engaged in strenuous physical activity at least three times per week at age 35 years revealed a decreased risk of breast cancer by 14 % compared with women who did not exercise. In the same study, a greater amount of total (baseline) physical activity was associated with a lower risk of breast cancer. Compared with no current physical activity, risk was reduced by 18, 11, 17, and 22 % for women who exercised 5.1–10, 10.1–20, 20.1–40, and > 40 metabolic equivalent task-hours/week (MET-h/wk). Eliassen et al. [8] conducted the largest prospective study in 95,396 postmenopausal women and documented 4,782 invasive breast cancer cases during a mean period of follow-up of 20 years. Compared with less than 3 MET-h/wk, women who were engaged in higher amounts of recent total physical activity (> 27 MET-h/wk) had a lower breast cancer risk by 15 %.

On the basis of accumulated scientific evidence, the WHO, in its recent guidelines, recognized that the increased level of physical fitness may reduce breast cancer risk by 20–40 % [1]. Furthermore, Friedenreich et al. [10] stated that ca. 165,000–330,000 cases of the six major cancers (breast, colon, lung, prostate, endometrium, and ovarian) could have been prevented each year in Europe alone if the population had maintained sufficient levels of physical activity. The above data are very important because physical inactivity is a modifiable risk factor and women who improve their exercise habits may substantially reduce the morbidity and mortality risk of the disease.

Exercise and rehabilitation of breast cancer

In most women, the level of physical activity decreases after cancer diagnosis and remains low several months after the completion of the therapy. Breast cancer survivors, on average, decreased their total postdiagnosis physical activity levels by 2 h per week, compared with physical activity levels reported in the year before diagnosis [11]. Irwin et al. [12] reported that, compared with women who were inactive both before and after diagnosis, women who increased physical activity after diagnosis had a 45 % lower risk of death and women who decreased physical activity after diagnosis had a fourfold greater risk of death.

However, only 32 % of breast cancer survivors participated in recommended levels of physical activity defined as 150 min per week of moderate to vigorous intensity sports/recreational physical activity after completing treatment [13]. The majority of this population should follow systematic exercise in order to obtain numerous physiological and psychological benefits. These include reductions in fatigue and improvements in immune function, physical functioning, body composition, and quality of life [14–16].

Exercise and mortality risk

Several studies demonstrated that systematic exercise and increased levels of physical fitness after diagnosis are associated with a better prognosis (decreased risk of recurrence and mortality) [12, 17–20]. These studies have demonstrated a 24–67 % reduction in the risk of total deaths and 50–53 % reduction in the risk of breast cancer deaths in women who are physically active after breast cancer diagnosis compared with sedentary women.

In the Nurses’ Health Study, compared with women who engaged in less than 3 MET-h/wk of physical activity, the adjusted relative risk of death from breast cancer was reduced by 20 % for 3–8.9 MET-h/wk, by 50 % for 9–14.9 MET-h/wk, by 44 % for 15–23.9 MET-h/wk, and by 40 % for ≥ 24 MET-h/wk (p = 0.004) [17].

Peel et al. [20] examined the association between cardiorespiratory fitness and risk of death from breast cancer in 14,811 women, aged 20–83 years, from the Aerobics Center Longitudinal Study. After controlling for confounders, women with high and moderate physical fitness levels had reduced breast cancer mortality risk by 55 and 33 %, respectively, compared with those in the lowest tertile during a follow-up period of 16 years (Fig. 1).

Fig. 1
figure 1

Survival free of breast cancer according to the levels of cardiorespiratory fitness (CRF) of the patients [20]

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Holick et al. [18] prospectively examined the relation between postdiagnosis recreational physical activity and risk of breast cancer death. Compared with women expending less than 2.8 MET-h/wk in physical activity, women who engaged in greater levels of activity had a significantly lower risk of dying from breast cancer (− 35 % for 2.8–7.9 MET-h/wk, − 41 % for 8.0–20.9 MET-h/wk, and − 49 % to − 0.89 for ≥ 21.0 MET-h/wk).

In another study, compared with inactive women, the multivariable hazard ratios for total deaths for women expending at least 9 MET-h/wk (approximately 2–3 h/wk of brisk walking) were reduced by 31 % for those active in the year before diagnosis and by 67 % for those active 2 years after diagnosis [12]. According to the relevant literature, the expected reduction in morbidity after exercise training was observed in pre- and postmenopausal women, overweight and normal weight women, and women with stage I–III of cancer.

Mechanisms of exercise

Exercise may influence breast cancer risk and recurrence of breast cancer through several mechanisms (Fig. 2). The most studied include sex steroid hormones (i.e., estrogens and androgens), insulin resistance, metabolic hormones (i.e., leptin, adipokines) and growth factors, inflammation markers (i.e., prostaglandin, C-reactive protein), immunological parameters (i.e., natural killer cells, leukocytes, T helper cells), and oxidative stress indexes (i.e., reactive oxygen species). Exercise training has the potential to positively affect all these biomarkers [4, 21–23], contributing significantly to the improved prognosis of the patients. However, there is a need to further examine whether exercise is equally beneficial in specific breast tumor types (invasive vs noninvasive or inflammatory breast cancer) or if the exercise-induced adaptations differ according to hormone receptor status, histology or tumor grade. For example, in the California Teachers Study [6], the researchers found a clear reduction of ER−/PR− (ER, estrogen receptor; PR, progesterone receptor) cancer risk but not of ER+/PR+ or ER+/PR− risk with increased levels of physical activity, whereas others found no reduction of ER+/PR − carcinoma risk in physically active women [24].

Fig. 2
figure 2

Biological mechanisms showing how exercise reduces the risk of breast cancer. BMI body mass index, SHBG sex hormone-binding globulin, TNF-a tumor necrosis factor-alpha, IL-6 interleukin 6, IGF-1 insulin-like growth factor 1 [25]

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Furthermore, some studies provided evidence that exercise, in postdiagnosis animal models of carcinogenesis, is associated with inhibition of primary tumor growth and a decrease in metastatic dissemination [26, 27]. These findings have important implications and may allow for using exercise as a complement in order to improve the efficacy of conventional cancer therapies. However, the exact molecular pathways that could explain the beneficial effects of physical training in both prevention and rehabilitation of breast cancer must be further clarified.

Exercise and lymphedema

Arm lymphedema is a chronic complication that affects a significant number of women treated for breast cancer. Upper extremity exercise has been traditionally avoided for women who have undergone surgical resection of the axillary lymph nodes or radiation therapy. Recent studies, however, indicated that upper body exercise (aerobic and/or resistance training) does not contribute to the onset or worsening of lymphedema among breast cancer survivors [28–31]. In a recent, well-controlled study, Schmitz et al. [32] evaluated the onset of lymphedema after one year of progressive weight-lifting program in breast cancer survivors. Women in the intervention group experienced a relative risk reduction of 35 % in the incidence of lymphedema, whereas greater improvements (risk reduction of 70 %) were seen among women with five or more lymph nodes removed.

Resistance exercise for breast cancer survivors

Recently, resistance exercise has gained popularity in breast cancer patients because several studies have indicated that this type of training is safe and has positive effects on body composition, physical functions, psychological outcomes (depression, anxiety, and self-confidence), and quality of life. Furthermore, this type of training can provide significant protection against the two major side effects of cancer therapy: muscle wasting and chronic fatigue [33–36]. In these patients, fatigue is a cause as well as a consequence of skeletal muscle wasting leading to a vicious cycle (fatigue–limited physical activity–deconditioning–worsening of fatigue), which adversely affects the clinical status and the outcome. Throughout specific resistance programs, patients can regain their muscle strength, reduce fatigue symptoms, and by this way, improve the activities of daily living.

Training recommendations

In order to substantially reduce the risk of breast cancer, women must follow 150 min per week of moderate to vigorous intensity sports/recreational physical activity. When prescribing exercise training to breast cancer patients, caution should be given to the specific side effects of anticancer treatment (lymphedema, easy fatigue, anemia, etc.). For example, women with lymphedema should wear a compression garment during exercise, especially during upper body training. Intensity depends on the physical fitness and the clinical status of the patient and must be kept between 50 and 75 % of VO2peak or 60 and 80 % of HRmax. The rate of perceived exertion should range from “fairly light” to “somewhat hard” on the Borg scale to fatigue (Table 1). With respect to the duration, the goal is to perform 30–45 min of continuous exercise; however, very few patients are able to achieve this target at the start of their rehabilitation program. For this reason, intermittent training has been used as a way to accumulating the appropriate exercise time, especially for the older and deconditioned patients. Regarding the modes of training, selection must be based on acute/chronic disease and treatment effects and participant preferences. Although walking and cycling are the most common modalities used in the literature, performing stretching and strengthening exercises can help patients to improve their flexibility and range of motion in the upper body [37, 38] (Table 1).

Table 1. Exercise recommendations to breast cancer patients [36, 37]
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Conclusion

Accumulated evidence clearly suggested that a higher level of physical fitness is associated with a significantly lower risk of breast cancer. Furthermore, regular exercise following a breast cancer diagnosis may be associated with substantial reductions in cancer-specific and all-cause mortality. Breast cancer survivors should follow systematic exercise during their rehabilitation in order to achieve a better recovery and to improve their health status, quality of life, and prognosis. Based on recent scientific evidence, a complete rehabilitation program for patients with breast cancer should combine both strength and aerobic exercise in order to maximize the expected benefits.