title: Predictors of aromatase inhibitor discontinuation as a result of treatment-emergent symptoms in early-stage breast cancer.
abstract: OBJECTIVE
  Aromatase inhibitors (AIs) are effective for treatment of hormone receptor-positive breast cancer, but adherence and persistence with therapy are poor. Predictors of treatment discontinuation are not clearly defined. It is unknown whether patients with intolerable toxicity from one AI are able to tolerate another.
  
  
  METHODS
  Women with early-stage breast cancer initiating AI therapy were enrolled onto a multicenter, prospective, open-label randomized trial of exemestane versus letrozole. Patients completed symptom questionnaires at baseline and serially during therapy. Patients who developed AI-associated intolerable symptoms and discontinued treatment were given the option to switch to the other study AI after a 2- to 8-week washout period.
  
  
  RESULTS
  Of the 503 enrolled women, 32.4% discontinued initial AI therapy within 2 years because of adverse effects; 24.3% discontinued specifically because of musculoskeletal symptoms. Median time to treatment discontinuation as a result of any symptom was 6.1 months (range, 0.1 to 21.2 months) and was significantly shorter in patients randomly assigned to exemestane (hazard ratio [HR], 1.5; 95% CI, 1.1 to 2.1; P = .02). Younger age and taxane-based chemotherapy were associated with higher likelihood of treatment discontinuation (HR, 1.4; 95% CI, 1.02 to 1.9; P = .04; and HR, 1.9; 95% CI, 1.00 to 3.6; P = .048, respectively). Of the 83 patients who chose to switch to the second AI, 38.6% continued the alternate AI for a median of 13.7 months.
  
  
  CONCLUSIONS
  Premature discontinuation of initial AI therapy as a result of symptoms is common, although more than one third of patients may be able to tolerate a different AI medication. Additional research is needed to identify predictive tools and interventions for AI-associated treatment-emergent symptoms.
authors.affiliation: University of MichiganComprehensive Cancer Center, Ann Arbor, MI, USA. norahh@med.umich.edu
authors.forename: N Lynn
authors.initials: NL
authors.lastname: Henry
authors.forename: Faouzi
authors.initials: F
authors.lastname: Azzouz
authors.forename: Zereunesay
authors.initials: Z
authors.lastname: Desta
authors.forename: Lang
authors.initials: L
authors.lastname: Li
authors.forename: Anne T
authors.initials: AT
authors.lastname: Nguyen
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lemler
authors.forename: Jill
authors.initials: J
authors.lastname: Hayden
authors.forename: Karineh
authors.initials: K
authors.lastname: Tarpinian
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Yakim
authors.forename: David A
authors.initials: DA
authors.lastname: Flockhart
authors.forename: Vered
authors.initials: V
authors.lastname: Stearns
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Storniolo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015897:Comorbidity; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077289:Letrozole; D055118:Medication Adherence; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000473:pathology; D009570:Nitriles / Q000627:therapeutic use*; D011379:Prognosis; D011446:Prospective Studies; D014230:Triazoles / Q000627:therapeutic use*; D028761:Withholding Treatment
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole; C056516:exemestane