Figure 5 – Germline-mediated immunoediting sculpts breast cancer subtypes and metastatic proclivity.

Schematic of mechanistic molecular model of germline-mediated immunoediting and its implications for improving breast cancer risk stratification. Briefly, during tumorigenesis, lesions with a high GEB in a gene of interest are less likely to acquire somatic amplification of that gene. However, if the tumor gains additional copies of the gene, it is forced to develop an immune suppressive/evasive phenotype and is more aggressive. Conversely, low GEB has little impact. By the time the tumor has metastasized to distant sites, it develops immune suppression/evasion mechanisms and is refractory to immunoediting pressures. In the pre-cancerous setting, GEB may be indicative of risk of progression to an invasive cancer since lesions with high GEB would have to overcome stronger immune pressures. Once the lesion becomes invasive, within a breast cancer subtype, tumors may be further stratified into those with high and low risk of relapse based on GEB in subtype-specific genes.