title: Patient-Reported Outcomes and Early Discontinuation in Aromatase Inhibitor-Treated Postmenopausal Women With Early Stage Breast Cancer.
abstract: Early discontinuation of aromatase inhibitors (AIs) is common and leads to poor outcomes but is challenging to predict. In the Exemestane and Letrozole Pharmacogenetics trial, a high rate of early discontinuation due to intolerance was observed. We hypothesized that early changes in patient-reported outcomes (PROs) predict AI discontinuation and that biochemical factors are associated with changes in PROs.
  
  
  
  Postmenopausal women with early-stage breast cancer enrolled in a prospective randomized trial of exemestane versus letrozole completed questionnaires at baseline and serially over 24 months to assess overall quality of life (EuroQOL Visual Analog Scale [VAS]); mood; and multiple symptoms, including a musculoskeletal symptom cluster. A joint mixed-effects/survival model was used to estimate the effect of the change in PROs on AI discontinuation. Associations between biochemical factors and change in PROs were examined.
  
  
  
  A total of 490 patients were analyzed. Worsening of EuroQOL VAS and the musculoskeletal cluster were associated with the highest risk for early discontinuation (hazard ratio [HR], 2.77 [95% confidence interval (CI), 2.72-2.81; p = .015]; HR, 4.39 [95% CI, 2.40-8.02; p < .0001], respectively). Pharmacokinetics and estrogen metabolism were not consistently associated with change in PRO measures. No clinically significant differences in any PRO between AIs were observed.
  
  
  
  Changes in PROs early during AI therapy were associated with treatment discontinuation. Identification of these changes could be used to target interventions in patients at high risk for early discontinuation.
  
  
  
  Early changes in patient-reported outcomes (PROs) can predict nonpersistence to aromatase inhibitor therapy. If used in clinical practice, PROs might identify women at highest risk for early discontinuation and allow for interventions to improve tolerance before significant toxicities develop. Further research is needed to improve capturing PROs in routine clinical practice.
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA.
authors.forename: Kunal C
authors.initials: KC
authors.lastname: Kadakia
authors.affiliation: Division of General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
authors.forename: Claire F
authors.initials: CF
authors.lastname: Snyder
authors.affiliation: Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
authors.forename: Kelley M
authors.initials: KM
authors.lastname: Kidwell
authors.affiliation: Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Seewald
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Flockhart
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Skaar
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Zereunesay
authors.initials: Z
authors.lastname: Desta
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Rae
authors.affiliation: Indiana University School of Nursing, Indianapolis, Indiana, USA.
authors.forename: Julie L
authors.initials: JL
authors.lastname: Otte
authors.affiliation: Indiana University School of Nursing, Indianapolis, Indiana, USA.
authors.forename: Janet S
authors.initials: JS
authors.lastname: Carpenter
authors.affiliation: Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Storniolo
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
authors.affiliation: Breast Cancer Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Vered
authors.initials: V
authors.lastname: Stearns
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA norahh@med.umich.edu.
authors.forename: N Lynn
authors.initials: NL
authors.lastname: Henry
mesh_terms: D047072:Aromatase Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D000071066:Patient Reported Outcome Measures; D017698:Postmenopause; D011446:Prospective Studies
chemical_list: D047072:Aromatase Inhibitors; D004967:Estrogens
keywords: Aromatase inhibitors; Early discontinuation; Patient-reported outcomes; Quality of life