Physical activity, diet, adiposity and female breast cancer prognosis: A review of the epidemiologic literature

Abstract

Given the increasing numbers of long-term survivors of breast cancer, research specific to prevention of recurrence, new breast cancer events, and mortality is of considerable public health importance. The objective of this report is to present a review of the published epidemiologic research on lifestyle and breast cancer outcomes among women with a history of breast cancer. This review focused on physical activity, diet, and adiposity; and the primary outcomes were additional breast cancer events and mortality. The most consistent finding from observational studies was that adiposity was associated with a 30% increased risk of mortality. Although the observational data were not as consistent (or abundant), physical activity appeared to be associated with a 30% decreased risk of mortality. These data do not indicate that alcoholic drinks are a risk factor. Based only on the observational studies, total dietary fat appeared to be a risk factor, fiber was protective, and information on micronutrients and specific foods was sparse. However, the null results of 2 dietary intervention trials in survivors suggests that lowering fat intake or increasing consumption of fruits, vegetables, and fiber will not lead to improved prognosis in breast cancer survivors. Given that a high proportion of breast cancer patients appear to be both sedentary and obese/overweight, clinical trials are needed to investigate whether the combination of increased physical activity and reduced adiposity can improve breast cancer prognosis.

Introduction

Advances in diagnosis and treatment have rendered breast cancer a chronic disease in countries with modern health care. For example, the American Cancer Society estimates that 89% of US women diagnosed with invasive breast cancer in 2009–2010 will be alive 5 years after diagnosis and 82% will be alive 10 years after diagnosis [1]. The National Cancer Institute estimates that approximately 2.5 million women with a history of breast cancer were alive in January 2006. However, little is known about lifestyle factors that modify breast cancer prognosis. Given the increasing numbers of long-term survivors, research specific to prevention of recurrence, new breast cancer events, and mortality is of considerable public health importance.

There are numerous reviews and meta-analyses addressing lifestyle and incident cancer. The most comprehensive and detailed synthesis of the scientific evidence regarding the extent to which lifestyle could modify the risk of cancer was published in 2007: Report on Food, Nutrition, Physical Activity and the Prevention of Cancer: a global perspective [2]. For this report, an expert panel was convened to assess and judge the evidence. The panel produced a set of public health goals and recommendations as follows:

• Be as lean as possible within the normal range of body weight.

• Be physically active as part of everyday life.

• Limit consumption of energy-dense foods and avoid sugary drinks.

• Eat mostly foods of plant origin.

• Limit intake of red meat and avoid processed meat.

• Limit alcoholic drinks.

• Limit consumption of salt and avoid mouldy cereals (grains) or pulses (legumes).

• Aim to meet nutritional needs through diet alone.

The expert panel also concluded that the evidence on survivorship was not clear enough to make firm judgments. Therefore, a special recommendation was made for cancer survivors indicating that they should follow the recommendations for cancer prevention.

In addition to the general recommendations given above for all cancers, this 2007 report reviewed the evidence regarding lifestyle and breast cancer. The panel considered the evidence for pre-menopausal cancer separately from post-menopausal cancer. For pre-menopausal breast cancer, the panel concluded the evidence was convincing that alcoholic drinks increased risk, probable that body fatness increased risk, and suggestive that low physical activity increased the risk of cancer. For post-menopausal cancer, the panel concluded that the evidence was convincing that alcoholic drinks and fatness increased risk; probable that low physical activity, abdominal fatness, and adult weight gain increased risk; and suggestive that total dietary fat increased risk of cancer. Overall, evidence regarding dietary factors (with the exception of total fat) was deemed limited.

There is considerable research on mechanisms for how lifestyle factors could influence breast cancer, although it is generally not specific to survivorship. Breast cancer is hormone related and the association between endogenous sex hormone concentrations and breast cancer risk in post-menopausal women is well-established. In particular, a recent meta-analysis reported that estradiol was associated with a 2- to 3-fold increased risk of breast cancer (p < 0.01) [3]. Chronic hyperinsulinemia is associated with increased availability of IGF-1 and concomitant changes in the cellular environment that favor tumor formation. Epidemiologic studies have shown a consistent, positive association of fasting insulin concentrations or type 2 diabetes mellitus with incident [4], [5] and recurrent breast cancer [6], [7]. Finally, inflammation in the tumor microenvironment appears to aid in the proliferation and survival of malignant cells, promote angiogenesis and metastasis, subvert adaptive immune responses, and alter responses to hormones and chemotherapeutic agents [8]. Dozens of circulating markers of inflammation have been identified, including adiponectin, IL-6, and TNF-α. High-sensitivity C-reactive protein (CRP) is a general marker of chronic inflammation at the vascular level that has been investigated extensively in relation to cardiovascular disease [9], [10], [11], [12] and more recently associated with increased cancer risk [13]. Notably, one recent study found that elevated CRP was associated with reduced survival in breast cancer patients [14].

Although the data are conflicting, research indicates that lifestyle can influence the mechanisms summarized above. In particular, obesity has been consistently correlated with higher concentrations of estradiol, fasting insulin, and inflammatory markers [15]. Randomized trials have shown that increased physical activity and diets low in fat and high in vegetables and fruit reduce circulating levels of estradiol and estrone [16], [17]. Physical activity, hypocaloric diets, and possibly low-glycemic diets may reduce fasting insulin levels [18]. Physical activity and dietary patterns characterized as Mediterranean, anti-inflammatory, or having a low glycemic load have been associated with reductions in CRP [19], [20]. These associations of obesity, physical activity, and diet with breast cancer markers suggest that lifestyle has the potential to modify breast cancer risk.

The objective of this report is to present a review of the epidemiologic research on physical activity, diet, and adiposity with breast cancer clinical outcomes among women with a history of breast cancer.