INS and breast cancer: If regulators of niches also function as mitogens for the reservoir of undetected, pre-invasive breast cancer lesions and/or dormant cancer stem cells [CSCs] within premalignant lesions in situ [124, 125]), then metformin's ability to decrease systemic metabolic biomarkers including insulin, IGF-1 and estradiol would regulate generation and/or maintenance of mammary stem cells and/or their niches.