**2. Physical activity and colon and breast cancer prevention**

#### **2.1 Colorectal cancer**

#### **2.1.1 Review of the evidence on physical activity and colon cancer prevention**

Colorectal cancer is the cancer for which there is the largest number of evidences on the beneficial effect of physical activity (Friedenreich et al., 2010;Roberts & Barnard, 2005). The overall level of scientific evidence on the beneficial effects of physical activity on the prevention of colon cancer is categorized as convincing (Friedenreich et al., 2010). This characterization is based on the definitions developed and used in the World Cancer Research Fund and American Institute for Cancer Research (the categories used are "convincing", "probable", "possible" and "insufficient"). Indeed on 51 studies conducted on colon and colorectal cancer, 43 demonstrated a reduction in cancer amongst the most physically active male and female participants with an average reduction from 20 to 30 % amongst both men and women. This protective effect of physical activity for colon cancer is not found for rectal cancer (Friedenreich et al., 2010).

A recent meta-analysis (Wolin et al., 2009) measured the magnitude of the inverse association between physical activity and risk of colon cancer restricting analyses to studies where data for colon cancer alone were available (exclusion of rectal cancer). A total of 52 studies were included, showing a 24% risk reduction overall, and generally similar risk reductions when men and women were examined separately.

Evidence for a dose-response effect exists with greater risks reductions observed for higher levels of physical activity (Friedenreich et al., 2010).

#### **2.1.2 What type of physical activity is associated with prevention of colon cancer ?**

Although each study quantified activity differently limiting the ability to draw conclusion about the amount of physical activity necessary for the 24% risk reduction observed in the meta-analysis of Wolin et al. (2009) one example provides information. In the Nurses' Health Study, women who expended more than 21.5 metabolic-equivalent task (MET) hours per week (MET-h/wk) in leisure-time physical activity had a risk ratio (RR) of colon cancer of 0.54 (95% CI, 0.33– 0.90), compared with women who expended less than 2 MET hours per week (Wolin et al., 2007). These levels are equivalent to brisk walking for some 5-6h per week in the most active and 0.5h per week in the least active. Interestingly, Wolin et al. (2009) were able to examine the effects of physical activity domain (occupational vs leisuretime) and found that the results were similar. Additional research are needed on the type, intensity and duration of physical activity that may afford the greatest risk reduction.

Overall, the results from all studies indicate a dose–response relation (higher levels of physical activity have been associated with a reduced risk of colon cancer) with risk reduction present across a wide range of physical activity frequency and intensity.

Although a physically active lifestyle might be associated with other healthful behaviours, a number of characteristics of the findings indicate that higher levels of physical activity directly prevent lower colon cancer. The association has been consistently reported in many studies of various designs, in diverse populations, for men and women, and after statistical control for a variety of other lifestyle factors. A compelling finding is that the inverse association has been observed for both leisure-time and occupational activities, for which patterns of potential confounding lifestyle characteristics are likely to differ.

The characteristics of physical activity which could have a protective effect towards colon cancer remained controversial, the data of the literature being contradictory. The categorizations and the methods of measure of physical activity which differ between studies are probably at the origin of these inconsistencies. Measuring physical activity in all its components, type, intensity and duration is complex. Although the results are heterogeneous, the available evidence suggest that at least 30-60 minutes per day of moderate to vigorous intensity for at least 5 days per week is required to significantly reduce the risk of colon cancer (Friedenreich et al., 2010).

Concerning the optimal period of life to practice physical activity to maximize its protective effect, the authors recommend a regular practice of physical activity throughout the life.

#### **2.2 Breast cancer**

110 Topics in Cancer Survivorship

on the current guidelines on physical activity for cancer prevention and for cancer survivors, with guidance based largely on proven associations that exist between physical activity and specific comorbid conditions (such as heart disease or osteoporosis) to which cancer survivors are especially prone, or associations between physical activity and other factors, such as quality of life, functional decline, and fatigue. Effective strategies to increase

**2. Physical activity and colon and breast cancer prevention** 

not found for rectal cancer (Friedenreich et al., 2010).

levels of physical activity (Friedenreich et al., 2010).

reductions when men and women were examined separately.

**2.1.1 Review of the evidence on physical activity and colon cancer prevention** 

Colorectal cancer is the cancer for which there is the largest number of evidences on the beneficial effect of physical activity (Friedenreich et al., 2010;Roberts & Barnard, 2005). The overall level of scientific evidence on the beneficial effects of physical activity on the prevention of colon cancer is categorized as convincing (Friedenreich et al., 2010). This characterization is based on the definitions developed and used in the World Cancer Research Fund and American Institute for Cancer Research (the categories used are "convincing", "probable", "possible" and "insufficient"). Indeed on 51 studies conducted on colon and colorectal cancer, 43 demonstrated a reduction in cancer amongst the most physically active male and female participants with an average reduction from 20 to 30 % amongst both men and women. This protective effect of physical activity for colon cancer is

A recent meta-analysis (Wolin et al., 2009) measured the magnitude of the inverse association between physical activity and risk of colon cancer restricting analyses to studies where data for colon cancer alone were available (exclusion of rectal cancer). A total of 52 studies were included, showing a 24% risk reduction overall, and generally similar risk

Evidence for a dose-response effect exists with greater risks reductions observed for higher

**2.1.2 What type of physical activity is associated with prevention of colon cancer ?**  Although each study quantified activity differently limiting the ability to draw conclusion about the amount of physical activity necessary for the 24% risk reduction observed in the meta-analysis of Wolin et al. (2009) one example provides information. In the Nurses' Health Study, women who expended more than 21.5 metabolic-equivalent task (MET) hours per week (MET-h/wk) in leisure-time physical activity had a risk ratio (RR) of colon cancer of 0.54 (95% CI, 0.33– 0.90), compared with women who expended less than 2 MET hours per week (Wolin et al., 2007). These levels are equivalent to brisk walking for some 5-6h per week in the most active and 0.5h per week in the least active. Interestingly, Wolin et al. (2009) were able to examine the effects of physical activity domain (occupational vs leisuretime) and found that the results were similar. Additional research are needed on the type, intensity and duration of physical activity that may afford the greatest risk reduction. Overall, the results from all studies indicate a dose–response relation (higher levels of physical activity have been associated with a reduced risk of colon cancer) with risk

reduction present across a wide range of physical activity frequency and intensity.

Although a physically active lifestyle might be associated with other healthful behaviours, a number of characteristics of the findings indicate that higher levels of physical activity

physical activity will be discussed.

**2.1 Colorectal cancer**

#### **2.2.1 Review of the evidence on physical activity and breast cancer prevention**

More than a dozen of cohort studies and an even more important number of case-control studies have examined the relations between physical activity and risk of breast cancer. More than three quarters of these studies have observed a beneficial of physical activity on breast cancer risk with a risk reduction about 25% when comparing the most to least active subjects. These results were confirmed and specified in a review of articles published between 1994 and 2006 on the relations between risks of breast cancer and physical activity (Monninkhof et al., 2007). The methodological quality of these articles was calculated on the basis of a statistical quality score and only articles of high quality were eligible: 19 cohort studies and 29 case-control studies. The higher quality cohort studies showed a risk reduction ranging from 20 to 40%. A more recent overview of the existing evidence relating physical activity to breast cancer risk has been recently published (73 studies) (Friedenreich et al., 2010). They found a consistent reduction of about 25% of breast cancer risk when comparing the most to least active study participants (Friedenreich et al., 2010). Moreover, there is consistent evidence of a dose-response effect of decreasing risk with increasing activity levels.

#### **2.2.2 What type of physical activity is associated with prevention of breast cancer ?**

Most studies have investigated the association between breast cancer and leisure physical activity (walking, cycling, swimming, gymnastics) but few studies have included low intensity leisure physical activity such as gardening, home repair, stair climbing or housework (cleaning, washing, cooking, child care…) which probably led to an underestimation of total energy expenditure, especially among women who do not have access to a sport activity. The inclusion in the physical activity questionnaires of household activity is important because it is one of the main sources of physical activity for women in most developed countries. This is highlighted in the European cohort EPIC (The European Prospective Investigation into Cancer and Nutrition study), which showed that the risk of breast cancer was reduced in women in the top quartile of household activities (>90 METh/wk) compared with women in the lowest quartile activities (<28 MET-h/wk): -19% for

Physical Activity and Cancer: It is Never Too Late to Get Moving! 113

At least seven prospective studies have investigated the relations between physical activity

The cohort of the Nurses' Health Study (121 700 women followed since 1976) has been the support of the first important study. This study focused on 2987 women with 280 breast cancer deaths and 8 years median follow-up (Holmes et al., 2005). Physical activity was measured by questionnaire every 2 years. The risk of death by breast cancer or breast cancer recurrence was reduced by 20 to 50% among women who walk 3 to 5 h per week (compared to those who walk less than 3 h per week). There was also a reduced risk of breast cancer

The collaborative Women's Longevity Study (CWLS) of 4482 women with breast cancer followed for 6 years with 109 deaths reported a comparable decreased risk of breast cancer death and total death (Holick et al., 2008). These results were confirmed by the Women's Healthy Eating and Living Study (WHEL study) which reported a relative risk of recurrence reduced to 0.56 for women walking 30 minutes a day 6 times per week (Pierce et al., 2007). Two smaller sized cohorts reported a decreased risk for total mortality but not breast cancer mortality with greater physical activity: the Life after Cancer Eidemiology (LACE) (Sternfeld et al., 2009) and the Health, Eating, Activity and Lifestyle (Heal) study (Irwin et al., 2008).

Three studies investigated the effects of exercise on cancer survival in patients diagnosed with colon (Meyerhardt et al., 2006a) or colorectal cancer (Haydon et al., 2006;Meyerhardt et

Meyerhardt et al. (2006a) demonstrated that disease-free colon-cancer survival improved with increasing levels of physical activity (p trend <0.01). Based on the results of this study, it is suggested that a protective HR is observed with >18 total MET-h/wk or equivalent (HR= 0.51; 95% CI: 0.26–0.97, for 18 to 26.9 MET-h/wk); the protective HR does not improve

Two studies investigated the effect of physical activity on mortality in patients diagnosed with colorectal cancer. Haydon et al. (2006) demonstrated that persons who exercised at least once a week had improved disease-specific survival (HR = 0.73; 95% CI: 0.54–1.00, p = 0.05). The benefit of physical activity was largely confined to stage II–III tumours (HR = 0.49; 95% CI: 0.30–0.79, p = 0.01), while no association was seen in stage I (least severe) or stage IV (most severe) tumours. The results of the study by Meyerhardt et al. (2006b) supported the role of post-diagnosis physical activity in decreasing cancer-specific mortality (p for trend = 0.008) and overall mortality (p for trend= 0.003) (cohort of the Nurses' Health Study: 573 women whose colon cancer has been diagnosed (stage I, II or III), followed on average 9.6 years). Pre-diagnosis level of physical activity was not found to be predictive of mortality, whereas women who increased their activity level after diagnosis had an HR of 0.48 (95% CI: 0.24–0.97) for colorectal-cancer deaths and an HR of 0.51 (95% CI: 0.30–0.85) for all-cause mortality versus those with no change in activity. In contrast, among women who decreased their activity level there was a modest, though non-significant, increase in both cancer-

All of these studies suggest that physical activity may confer additional benefits to those of the surgery, radiation therapy and/or chemotherapy for survival after treatment of breast or colon cancer. However, these results are observational and cannot formally identify a relationship of cause and effect. However the number of randomized trials

**3.1 Physical activity and breast cancer survival** 

recurrence and total mortality (Holmes et al., 2005).

**3.2 Physical activity and colon cancer survival** 

al., 2006b).

beyond 27 MET-h/wk.

specific and overall mortality.

and breast cancer survival (for a review see Barbaric et al., (2010).

postmenopausal women (HR: 0.81; 95%CI, 0.70-0.93) and -29% for premenopausal women (HR: 0.71; 95%CI, 0.55-0.90) (Lahmann et al., 2007). These results based on a large and heterogeneous cohort (218 169 women from nine European countries, aged 20 to 80 years at baseline followed for an average period of 6.4 years) and which used standardized data collection of physical activity and that could control for all the potential confounding factors, provide additional evidence that moderate forms of physical activity, such as household activity, may be more important than less frequent more intense recreational physical activity in reducing breast cancer risk.

Similarly, E3N French study, which is the French part of the EPIC, refers to a decrease in the relative risk of 18% when household activities are of light intensity while this decline is 38% when the activity is of high intensity (Tehard et al., 2006), a dose-response effect being also shown for these household activities. A negative trend in risk of breast cancer associated with total recreational activity (p trend <0.01) and total physical activity (p trend <0.05) was also observed.

Moreover, in review of Monninkhof et al. (2007), a trend analysis showed that the risk of developing breast cancer decreased by 6% per hour of physical activity added per week (assuming that the activity would be sustained over a long period of time) showing that this is the total amount of physical activity which is essential.

Overall, the analysis of the literature shows that at least 4 to 7 hours per week of moderate to vigorous physical activity would be required to produce a statistically significant decrease of the risk of breast cancer.

Several studies have attempted to determine the existence of a period of life in which the protective effects of physical activity would be maximum. In the absence of conclusive studies (pubertal period for some practice, adulthood for others), sustained lifetime physical activity appears as the most suitable preventive means (Friedenreich et al., 2010).

#### **2.3 Summary of the evidence on the protective effects of physical activity on colon and breast cancer**

The available evidence suggest that:

