A number of studies have assessed the effect of weight change during lifetime on breast cancer risk. The majority of studies pertain to postmenopausal breast cancer and show an increased risk with weight gain after 18 years of age; the effect over adulthood is estimated at 5% per 5 kg of weight gain [56, 64]. Furthermore, weight gain after menopause has been also found to independently increase breast cancer risk (OR: 1.18 for weight gain of at least 10 kg compared to women with no weight change) [64]. It is worth noting, however, that periods of potential weight loss have not been taken into account. The published data for premenopausal breast cancer are limited. In one report no effect was found [65], whereas another study showed a marginally significant decrease in breast cancer risk among women reporting weight loss since the age of 18 years [66].

Of interest is also the association of breast cancer with fat distribution, besides overall adiposity. Central adiposity is linked to metabolic-hormonal changes leading to insulin resistance, as well as hyperandrogenemia and excess conversion of peripheral androgens to oestrogens. Waist-to-hip ratio is considered a reliable measure of central adiposity and has been consistently associated with postmenopausal breast cancer [56, 67]. Again findings for premenopausal breast cancer remain inconsistent and inconclusive; as contrasted to BMI, however, two meta-analyses have shown an increased risk of premenopausal cancer in women with central adiposity [67, 68]. The results were heterogeneous, though, whereas the effect seemed to be stronger among women of Asian origin.

Physical activity is considered an established primary breast cancer prevention strategy for both premenopausal and postmenopausal women [69]; indeed, sustained regular activity throughout life seems to provide the highest benefit [70]. Noticeably, it has been estimated that elimination of physical inactivity would result in a decrease of breast cancer incidence by 10% [71]. The first study aiming to assess this association, using a detailed lifetime physical activity assessment, showed a 58% decreased risk of breast cancer among premenopausal women with an average of 3.8 h of exercise per week, compared to those who reported no exercise [72]. Similarly, a decreased risk by 45% for breast cancer in postmenopausal women in the highest physical activity category was found [73]. A large recent meta-analysis summarizing evidence from 31 cohort studies confirmed the results and showed an overall 13% decrease in risk among women reporting the highest versus the lowest level of physical exercise. A dose-response pattern was recorded, and the overall estimate was stronger for premenopausal women and women with normal BMI values, compared to overweight, and confined to oestrogen/progesterone receptor-negative tumours [74]. Interestingly, in a systematic review of the literature, occupation-related, household, recreational and walking-associated physical activity all seemed to independently decrease the risk for breast cancer [75].

The adverse effects of obesity and the beneficial actions of physical activity are generally considered to be exerted via common mechanisms. The proposed actions could be generally synopsized as (a) exposure to oestrogens, (b) changes in insulin-related factors and adipokines and (c) anti- or pro-inflammatory actions and other protective mechanisms. These are described below.

Diet has been associated with the development or progression of major human cancers, including breast, prostate and colorectal tumours. It is a modifiable factor, which has been the subject of intensive research interest as it provides a window for preventive intervention strategies, due also to the immense interest of lay people in associating their dietary habits with cancer risk and breast cancer risk, in particular.

Breast cancer remains the leading type of malignancy in women worldwide with a profoundly higher incidence in the developed compared to developing countries. Increasing trends have been evident in Western communities for several decades. Lifestyle changes leading to obesity and physical inactivity, higher alcohol consumption and variable use of exogenous oestrogens are believed to have contributed to the observed increase of the disease. Higher oestrogen exposure, indicated by proxies, such as earlier age at menarche, later menopause and adverse childbearing patterns, has been witnessed in parallel [107]. There is no strong evidence that other macro- or micronutrients are clearly included in the aetiology of the disease.

Intense research over the last few decades has broadened our understanding of the aetiology of the disease and revealed modifiable factors offering applicable preventive targets (◘ Fig. 4.2). According to the World Cancer Research Fund, 40% of postmenopausal breast cancers would have been prevented, where it is possible to reduce alcohol consumption, physical inactivity and obesity [41]. In order to formulate public health recommendations and tangible prevention guidelines, future research should focus on specific components of modifiable risk factors, such as type and timing of physical activity, and their geographical, ethnical and cultural customization. Indispensable is further exploration of the model of oestrogen- or other hormone-induced carcinogenesis, the findings of which should be clinically integrated into breast cancer prevention and control programmes.