The randomized phase III BOLERO-2 trial showed the efficacy of everolimus in combination with exemestane in patients with ER-positive/HER2-negative advanced breast cancer resistant to AIs with a significant improvement in PFS (HR = 0.43, 95% CI 0.35–0.54, p < 0.001) compared to exemestane monotherapy [104]. Here, ESR1 is linked to breast carcinoma.