In this context, recently, the results of a study involving 674 metastatic HR-positive/HER2-negative breast cancer patients randomized to receive either the aromatase inhibitor anastrozole plus selective ER down regulator fulvestrant with anastrozole alone as the first-line therapy: the median overall survival was 49.8 months in the combination-therapy groups and 42.0 months in the anastrozole alone group [512]. Here, ESR1 is linked to breast cancer.