In the MA.32 phase 3 randomized, double-blind, placebo-controlled trial involving 3649 non-diabetic patients with high-risk operable breast cancer, adjuvant metformin (850 mg twice daily for 5 years) failed to show a significant improvement in invasive disease-free survival compared to the placebo, with no benefit observed in either hormone receptor-positive or -negative subgroups [117]. Here, NR4A1 is linked to breast cancer.