Can Living a Less Sedentary Life Decrease Breast Cancer Risk in Women?

“Sedentary behavior has been independently associated with chronic disease-related risk factors such as central adiposity, insulin resistance and chronic inflammation, factors hypothesized to be operative in the development and progression of breast cancer.”

The first investigators to examine if physical activity might reduce breast cancer risk were Frisch and colleagues in 1985, who found that their study population of former college athletes had a lower lifetime prevalence of breast cancer and other reproductive cancers [1]. Since that first publication, there has been a veritable explosion of research activity in this field with more than 100 papers published worldwide that have examined some aspect of physical activity and its relation to breast cancer risk. From this initially crude classification of physical activity [1], more sophisticated studies, including some that have assessed lifetime physical activity, have been conducted. Overall, there is now consistent and convincing evidence that physical activity reduces the risk of breast cancer by, on average, 25% when comparing the most and least active study participants in these observational studies [2]. Furthermore, there is also consistent evidence of a dose-response effect between higher levels of activity and increasingly lower rates of breast cancer risk. More recent epidemiologic research on this topic is addressing the questions of what type (i.e., occupational, household or recreational) and dose (i.e., frequency, intensity and duration) of exercise are most beneficial for breast cancer risk reduction, as well as the timing in life when physical activity has the greatest impact on lowering breast cancer risk. Although all types of activity are associated with breast cancer risk decreases, somewhat stronger effects have been observed for recreational and household activities (21% average decreased risk). Effects are also stronger for activities carried out over the entire lifetime (27% decreased risk) or after menopause (31% decreased risk) [2]. Regarding the dose of activity required for breast cancer risk reduction, the intensity of the activity must be at least moderate (three to six metabolic equivalent tasks) or vigorous (more than six metabolic equivalent tasks), where one metabolic equivalent task is equivalent to the energy expenditure at rest, which is estimated as 3.5 ml of oxygen per kilogram of bodyweight per minute (3.5 ml/kg/min) for a 70-kg (150-1b) person [3]. Activities that are carried out more frequently and of a longer duration were also observed to be of greater benefit [2]. Across these studies, 2–3 h/week of activity reduced risk, on average, by 7%, whereas 6.5 h/week was associated with a 28% risk reduction [2].

Given the large number of studies that have been conducted, it is now possible to identify subgroups of the population that may benefit particularly from physical activity. A stronger effect of physical activity for breast cancer risk reduction has been observed in normal weight women, non-Caucasians, women without a family history of breast cancer and parous women [2]. Several aspects of the association between physical activity and breast cancer risk remain unclear, including whether or not the benefit of activity depends on the histologic type of the tumor, the hormone receptor status and/or other individual molecular aspects.

“Despite the lack of epidemiologic evidence, there is a sound biologic rationale for why sedentary behavior might contribute to breast cancer risk.”

Several hypothesized biologic mechanisms exist to explain how physical activity reduces breast cancer risk, including possible effects of exercise on endogenous sex steroid hormones and body fat levels, insulin resistance, and inflammation. Randomized controlled exercise intervention trials are investigating exactly how exercise influences these mechanisms, and emerging evidence shows a direct effect of exercise on the following mechanisms: estradiol and sex hormone-binding globulin [4–6]; leptin, insulin and homeostasis model assessment of insulin resistance levels [7]; total body fat, specifically intra-abdominal and subcutaneous fat [8]; C-reactive protein levels [9]; and oxidative stress levels [10]. Research studies are ongoing to determine the exact dose of physical activity that is needed to influence these biomarkers and thereby reduce breast cancer risk. Current public health recommendations developed by different national and international agencies for physical activity for cancer risk reduction advocate for at least 4–7 h/week of moderate-to-vigorous intensity activity [11,12].

“More recently, there has been research interest in considering not only the benefits of increased activity, but also the risks associated with too much sedentary behavior.”

Considerable evidence exists from observational epidemiologic studies that obesity after menopause and weight gain over the lifetime increase breast cancer risk by an average of 50% for a BMI greater than 30 kg/m². At this level of risk increase, and given the prevalence of obesity in north America and Europe, over 20% of breast cancers in these regions could be attributed to obesity [13]. Relatively limited research has examined how weight loss might influence breast cancer risk. Intentional weight loss ranging from 5 to more than 15% of body weight has been associated with a greater than 50% decrease in breast cancer risk in two cohort studies that have examined this topic [14,15]. The most effective means of achieving weight loss that may influence breast cancer risk has been recently shown to be a combination of caloric restriction and increased physical activity, and the exact biologic mechanisms involved in either dietary change, increased physical activity or a combination of these two risk factors is being investigated [16].

To date, public health recommendations on the amount of physical activity needed to reduce breast cancer risk have been based entirely on observational studies, because no randomized controlled trials have been conducted for exercise with breast cancer incidence as the primary outcome. The large sample size required for a study of physical activity and weight control for breast cancer prevention, ranging from 25,000 to 30,000 depending on the amount of risk reduction assumed, has been the main impediment for launching such a trial to date.

Currently, clinical options for breast cancer prevention are limited to chemoprevention, prophylactic mastectomy and/or bilateral oopherectomy. Such measures are usually reserved for high-risk women, such as carriers of genetic mutations and women of Ashkenazi Jewish heritage. However, even for these women, the side effects of such preventive measures remain a deterrent. Hence, there is growing public and professional health awareness of the potential benefits of promoting physical activity as a healthy, safe and achievable means of reducing breast cancer risk in women.

More recently, there has been research interest in considering not only the benefits of increased activity, but also the risks associated with too much sedentary behavior. Sedentary behavior describes prolonged sitting or reclining, characterized by low energy expenditure, and is distinct from physical inactivity (the absence of health-enhancing physical activity) [17]. Sedentary behavior has been independently associated with chronic disease-related risk factors such as central adiposity, insulin resistance and chronic inflammation, factors hypothesized to be operative in the development and progression of breast cancer [17].

Cross-sectional analyses from the National Health and Nutrition Examination Survey 2003–2006 demonstrated positive associations between accelerometer-assessed sedentary time and breast cancer biomarkers (BMI, waist circumference, C-reactive protein, insulin, homeostasis model assessment of insulin resistance), independent of moderate-to-vigorous physical activity and other confounders. Furthermore, the manner in which sedentary time was accumulated through the day seemed to have implications for breast cancer risk: accruing sedentary time in longer bouts was associated with higher BMI [18].

“…the benefits of decreased sedentary behavior and increased physical activity extend well beyond breast cancer risk reduction, and the adverse side effects are negligible.”

To date, few epidemiologic studies have examined the association between sedentary behavior and breast cancer risk. Neither self-reported Television viewing nor overall sitting time were associated with invasive or in situ breast cancer in the NIH – AARP Diet and Health study [19]. Similarly, no statistically significant association between television viewing and breast cancer was found in a case–control study of 3739 Indian women [20].

Despite the lack of epidemiologic evidence, there is a sound biologic rationale for why sedentary behavior might contribute to breast cancer risk. There is clearly a need for further epidemiologic studies to determine the extent of this association, but future studies would benefit from improved methods of sedentary behavior measurement. Studies to date have been limited by use of crude items that ask participants to recall total sitting time or television viewing time per day. Objective measurement of sedentary behavior by accelerometers offers many advantages and should be incorporated into future studies wherever possible; however, these methods cannot differentiate between different contexts or types of sedentary behaviors. Hence, there is also a need for the development and validation of comprehensive self-report measures of sedentary behavior across different domains.

Can leading a less sedentary life reduce breast cancer risk? The evidence accumulated to date suggests that the answer is ‘yes‘. Importantly, the benefits of decreased sedentary behavior and increased physical activity extend well beyond breast cancer risk reduction, and the adverse side effects are negligible. It is safe to advise all women to become more active in their daily lives through a combination of spending less time sitting and more time standing, walking and engaging in whatever physical activity they can manage. Additional health benefits, and greater decreases in breast cancer risk, will be achieved by participation in regular, moderate-to-vigorous intensity exercise.