ABSTRACT
Although less than 5% to 10% of breast cancer cases are attributable to BRCA1 and BRCA2 mutations, the risk of breast cancer in known BRCA1 and BRCA2 heterozygotes is substantial. Estimates vary, but the recently reported lifetime breast cancer risk for
BRCA1 mutation carriers in a combined analysis of data from 22 studies of case series unselected for family history is 65% (1-3). The burden of this risk in BRCA1 mutation carriers begins at a young age with premenopausal BRCA1 mutation carriers facing between 17-and 32-fold higher breast cancer risk than age-matched controls in the
general population. The risk plateaus as age increases but continues through the post-
menopausal years, with BRCA1 mutation carriers aged 60 to 69 facing 14-fold higher risk than age-matched controls in the general population. The estimated lifetime breast cancer
risk in BRCA2 mutation carriers from the combined analysis is lower, at approximately 45%, although still significantly greater than that of the general population. For BRCA2 mutation carriers, the breast cancer risk increases with age and is greatest during the
postmenopausal years (3). This significant extent of breast cancer penetrance in BRCA1/2 mutation carriers has led to the development of prevention and early detection interventions
for this high-risk population. These interventions are reviewed in this chapter.
