Recent advances in the genetics of susceptibility to and treatment of breast cancer

Recent large-scale GWAS have identified a number of genes that modestly increase the risk of sporadic breast cancer and modify the risk of cancer in individuals carrying BRCA1 or BRCA2 mutations. These genes were not previously implicated in breast cancer pathogenesis and provide new insights into the aetiology of the disease as well as a means of defining new potential therapeutic targets and refining risk estimates. Three categories of genes relevant to breast cancer aetiology can now be defined (see Table 1): highly penetrant genes (e.g. BRCA1 and BRCA2) that confer a high risk of cancer; rare mutations in genes (e.g. ATM and BRIP1) that moderately increase risk by 2- to 4-fold; and common variants in a number of genes mainly identified by GWAS (e.g. FGFR2) that increase cancer risk by less than 2-fold. Further genes that affect breast cancer risk exist and interrogation of the huge datasets generated by GWAS and in larger patient cohorts with different characteristics will provide more detailed molecular phenotypes to define breast cancer susceptibility and inform future clinical management strategies. It is likely that CYP2D6 genotyping will be introduced into mainstream clinical practice to determine tamoxifen efficacy. Pharmacogenetics will be increasingly used in breast cancer management to more accurately tailor medication to the individual, to reduce side effects and to optimise outcome.