World Health Organization: High Risk Factors for Breast Cancer Several high-risk factors for breast cancer are well documented. However, specific high-risk factors cannot be identified for the majority of women who develop breast cancer. A family history of breast cancer can double or triple the risk. Some mutations, particularly in BRCA1, BRCA2 and p53, produce a high risk of breast cancer. However, these mutations are rare and account for a small percentage of the total breast cancer burden. Reproductive factors associated with chronic exposure to endogenous estrogens, such as early onset of menarche, delayed menopause, and advanced age at first birth, are several of the most important risk factors for breast cancer. Exogenous hormones also produce a higher risk of breast cancer. Users of oral contraceptives and hormone replacement therapy are at higher risk than non-users. Breastfeeding is protective Danaei et al. calculated the effect of various modifiable risk factors (excluding reproductive factors) on the total burden of breast cancer. They concluded that 21% of all breast cancer deaths worldwide could be attributed to alcohol consumption, excess weight and obesity, and lack of physical activity. This proportion was higher in high-income countries (27%), where the most important factors were excess weight and obesity. In low- and middle-income countries, the proportion of breast cancers attributable to these high-risk factors was 18%, with physical inactivity being the most important determinant (10%). The role of diet combined with later primiparity, fewer births, and shorter duration of breastfeeding may partially explain the differences in breast cancer incidence between developed and developing countries. The increasing adoption of Western lifestyles in low- and middle-income countries is an important determinant of the increased incidence of breast cancer in these countries.