CYP19A1 and breast cancer: Similarly, regardless of the supporting rationale of targeting mTOR signaling with metformin to circumvent breast cancer endocrine resistance, a randomized phase II study (N = 60) of aromatase inhibitors (exemestane or letrozole) plus metformin or placebo in pretreated postmenopausal women with ER+ metastatic breast cancer failed to demonstrate improved efficacy in terms of PFS or OS [118].