Risk of breast cancer recurrence in women initiating tamoxifen with CYP2D6 inhibitors

CRA508 Background: Tamoxifen (TAM) is metabolized to its active form, endoxifen, by hepatic cytochrome P450 (CYP) 2D6. Diminished CYP2D6 function, both by genetic variation or concurrent use of pharmacologic inhibitors, can significantly reduce endoxifen plasma concentrations and may lead to reduced TAM effectiveness. Methods: We interrogated an integrated research database comprised of de-identified medical and pharmacy claims (Rx) data for 10.7 million U.S. health plan members to identify women with breast cancer (BrCa) new to TAM therapy in a 30-month period from 2003 to 2005, and investigated the risk of recurrent BrCa as a function of concurrent use of potent and moderate inhibitors of CYP2D6. Inclusion criteria were: greater than or equal to 24 months of follow-up data and adherence to TAM (medication possession ratio > 70%) over 2 years (N = 1,298). Disease recurrence was defined by BrCa ICD-9 codes or CPT codes for mastectomy, lumpectomy, lymph node dissection, or radiation therapy occurring at le...