Unraveling the genetic etiology of mammographic breast density

CN12-03

One of the most important risk factors for breast cancer identified to date is mammographic breast density. Breast density reflects variation in fat, stromal and epithelial tissues on the mammogram. Women with high levels of breast density have a 3-6 fold increased risk of breast cancer compared to women with little to no breast density. Increased breast density is common in the population, quantifiable and potentially modifiable but the biology underlying this trait is largely unknown. Risk factors identified for breast density to date only account for 20-30% of variation in the trait. Genetics and the interaction between genes and environment are hypothesized to account for the remaining variation. Evidence for a genetic influence on breast density to date comes from familial aggregation, family-based segregation, twin, molecular epidemiology and genetic linkage studies. These data together imply that genes for breast density may predispose women to high density across the lifespan, translating to increased breast cancer risk. The use of intermediate phenotypes such as breast density to identify genes for breast cancer may allow for increased power since the number of genetic and environmental factors influencing each intermediate marker is likely smaller than that influencing the clinical endpoint, namely breast cancer. As such, the variation attributed to genetic loci influencing breast density will likely be greater than for genetic loci influencing breast cancer risk.
 This presentation will review the evidence for a genetic influence on breast density, discuss future genetic investigations and the importance of studying the genetic epidemiology of this marker of breast cancer risk.