ESR1 and neoplasm: Although we have shown this is true for grade, ER and HER2 status, it is likely that many other variables that were assessed (e.g. age, claudin-low status, tumor size) and or not assessed (e.g. tumoral heterogeneity, clonal complexity, lifestyle and information on exposure of the patient) can also affect the estimations of pathway activity using these tools [31–33].