Kadakia, Kunal C.Kidwell, Kelley M.Seewald, Nicholas J.Snyder, Claire F.Storniolo, Anna MariaOtte, Julie L.Flockhart, David A.Hayes, Daniel F.Stearns, VeredHenry, N. Lynn2019-04-172019-04-172017-07Kadakia KC, Kidwell KM, Seewald NJ, Snyder CF, Storniolo AM, Otte JL, Flockhart DA, Hayes DF, Stearns V, Henry NL. Prospective assessment of patient-reported outcomes and estradiol and drug concentrations in patients experiencing toxicity from adjuvant aromatase inhibitors. Breast Cancer Res Treat. 2017 Jul;164(2):411-419. doi: 10.1007/s10549-017-4260-2. Epub 2017 Apr 27. PubMed PMID: 28451964; PubMed Central PMCID: PMC5517133.https://hdl.handle.net/1805/18878PURPOSE: Aromatase inhibitors (AI), which decrease circulating estradiol concentrations in post-menopausal women, are associated with toxicities that limit adherence. Approximately one-third of patients will tolerate a different AI after not tolerating the first. We report the effect of crossover from exemestane to letrozole or vice versa on patient-reported outcomes (PROs) and whether the success of crossover is due to lack of estrogen suppression. METHODS: Post-menopausal women enrolled on a prospective trial initiating AI therapy for early-stage breast cancer were randomized to exemestane or letrozole. Those that discontinued for intolerance were offered protocol-directed crossover to the other AI after a washout period. Changes in PROs, including pain [Visual Analog Scale (VAS)] and functional status [Health Assessment Questionnaire (HAQ)], were compared after 3 months on the first versus the second AI. Estradiol and drug concentrations were measured. RESULTS: Eighty-three patients participated in the crossover protocol, of whom 91.3% reported improvement in symptoms prior to starting the second AI. Functional status worsened less after 3 months with the second AI (HAQ mean change AI #1: 0.2 [SD 0.41] vs. AI #2: -0.05 [SD 0.36]; p = 0.001); change in pain scores was similar between the first and second AI (VAS mean change AI #1: 0.8 [SD 2.7] vs. AI #2: -0.2 [SD 2.8]; p = 0.19). No statistical differences in estradiol or drug concentrations were found between those that continued or discontinued AI after crossover. CONCLUSIONS: Although all AIs act via the same mechanism, a subset of patients intolerant to one AI report improved PROs with a different one. The mechanism of this tolerance remains unknown, but does not appear to be due to non-adherence to, or insufficient estrogen suppression by, the second AI.en-USPublisher PolicyAromatase inhibitorsArthralgiaCrossoverPatient outcome assessmentQuality of lifeArticle