Breast cancer is the most common malignancy in females with more than 1,150,000 new cases diagnosed each year worldwide. Incidence of the disease is now declining in the USA due to a decline in the use of hormone replacement therapy . Advances in local and systemic treatment strategies have improved survival rates . The large number of long-term survivors has revealed the problem of contralateral breast cancer (CBC). Descriptive studies have shown the efficiency of contralateral prophylactic mastectomy (CPM) in preventing CBC . These data and the fear of patients for a new breast cancer in the unaffected breast probably explain the dramatic increase of a more aggressive surgery such as CPM in the USA . Does radiotherapy with internal mammary field contribute to increased risk of CBC? Does CPM assist patients or represents an overtreatment with harms for patients, society and public health? Can high-risk patients be identified before clinical occurrence  for risk stratification-based guided treatment to prevent CBC?