The daily vaginal application of ultra-low dose 0.03 mg E3 in postmenopausal women results only in a small and transient increase in serum E3, but serum levels of E1, E2, FSH, LH and SHBG are not influenced leading to the conclusion this therapy could be safe even in hormone sensitive BC patients [5, 13, 21]. The gene discussed is PLOD1; the disease is breast cancer.