Association Of A Low-Expression Slco1b1 Polymorphism With Estrogen Concentrations Before And During Aromatase Inhibitor Treatment For Breast Cancer.

543Background: Three aromatase inhibitors (AI), the steroid exemestane, and the azoles anastrozole and letrozole, are effective in the treatment of estrogen receptor positive (ER+) breast cancer by preventing biosynthesis of estrogens including estradiol (E2), estrone (E1), and estrone-sulfate (E1S) in postmenopausal women. OATP1B1, encoded by SLCO1B1, transports E1S into the liver for desulfation to active E1. Women carrying the low-expression SLCO1B1 rs4149056 single nucleotide polymorphism (SNP) have higher E1-conjugate levels (Dudenkov Breast Cancer Res Treat 2017). We hypothesized that patients carrying this SNP would have increased E1S at baseline, and this E1S reserve could resupply E1 and E2 resulting in detectable estrogen levels during AI treatment. Methods: Five hundred postmenopausal women with ER+ breast cancer were randomized 1:1 to either exemestane 25 mg/day or letrozole 2.5 mg/day. Plasma estrogen concentrations were measured prior to and after 3 months of AI treatment using LC/MS/MS (LLO...