Targeting downstream mTOR signaling via an mTORC1 inhibitor, everolimus, in combination with the aromatase inhibitor exemestane compared to exemestane plus placebo, improved the median progression-free survival (PFS) in ER+/HER2− advanced breast cancer from 3.2 to 7.8 months (hazard ratio 0.38 [95% CI 0.31–0.48], P < 0.0001) [28]. Here, ESR1 is linked to breast cancer.