ESR1 and breast cancer: Basically, the first step is fuzzy subtype identification by assessing the probability of a patient belonging to each of the three breast cancer molecular subtypes (ER-/HER2-, HER2+ and ER+/HER2-); the second step identifies the prognostic gene signatures specific to each subtype and/or uses existing signatures; and the third step combines the probabilities with the corresponding subtype signature scores, which then results in the final GENIUS risk prediction score.