Improving the risk assessment of inherited breast and ovarian cancer : clinical significance of BRCA1/2 variants and risk modifiers

Genetic screening of the BRCA1/2 genes is performed to members of families with early onset breast and/or ovarian cancer. Identification of the BRCA1/2-mutation carriers (at risk of early onset of breast and/or ovarian cancer and others in the case of male carriers) and non-carriers (which have the same risk as the general population) allows providing adequate clinical options to these individuals regarding cancer risk prevention and, eventually, prevention of transmission of the disease-causing variants to their offspring. However, accurate risk assessment is hampered by the difficulty to predict whether a woman will develop breast or ovarian cancer and the high number of variants of uncertain clinical significance identified during genetic screening, as it is not possible to determine if these are disease causing. This thesis compiles several studies that describe successful approaches for a more accurate cancer risk assessment of individuals from breast and/or ovarian cancer families.