title: Prospective characterization of musculoskeletal symptoms in early stage breast cancer patients treated with aromatase inhibitors.
abstract: OBJECTIVE
  Aromatase inhibitors (AIs) are increasingly used as adjuvant treatment of postmenopausal women with hormone receptor-positive breast cancer. AIs are commonly associated with musculoskeletal symptoms. The primary objective of this study was to describe the musculoskeletal symptoms that developed in the first 100 subjects enrolled who had at least 6 months follow-up.
  
  
  METHODS
  Women with early stage hormone receptor-positive breast cancer were recruited into a multicenter randomized clinical trial to study the pharmacogenomics of two AIs, exemestane, and letrozole. Patients completed the Health Assessment Questionnaire (HAQ) and Visual Analog Scale (VAS) at baseline, 1, 3, 6, and 12 months to assess changes in function and pain, respectively. Patients were referred for evaluation by a rheumatologist if their HAQ and/or VAS scores exceeded a predefined threshold.
  
  
  RESULTS
  Forty-four of 97 eligible patients (45.4%) met criteria for rheumatologic referral. Three patients were ineligible because of elevated baseline HAQ (2) and failure to initiate AI therapy (1). No baseline characteristics were significantly associated with referral. Median time to onset of symptoms was 1.6 months (range 0.4-10 months). Clinical and laboratory evaluation of patients evaluated by rheumatology suggested that the majority developed either non-inflammatory musculoskeletal symptoms or inflammation localized to tenosynovial structures. Thirteen patients discontinued AI therapy because of musculoskeletal toxicity after a median 6.1 months (range 2.2-13 months).
  
  
  CONCLUSIONS
  Musculoskeletal side effects were common in AI-treated patients, resulting in therapy discontinuation in more than 10% of patients. There are no identifiable pre-therapy indicators of risk, and the etiology remains elusive.
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109-0942, USA.
authors.forename: N Lynn
authors.initials: NL
authors.lastname: Henry
authors.forename: Jon T
authors.initials: JT
authors.lastname: Giles
authors.forename: Dennis
authors.initials: D
authors.lastname: Ang
authors.forename: Monika
authors.initials: M
authors.lastname: Mohan
authors.forename: Dina
authors.initials: D
authors.lastname: Dadabhoy
authors.forename: Jason
authors.initials: J
authors.lastname: Robarge
authors.forename: Jill
authors.initials: J
authors.lastname: Hayden
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lemler
authors.forename: Karineh
authors.initials: K
authors.lastname: Shahverdi
authors.forename: Penny
authors.initials: P
authors.lastname: Powers
authors.forename: Lang
authors.initials: L
authors.lastname: Li
authors.forename: David
authors.initials: D
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
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Clauw
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D047072:Aromatase Inhibitors / Q000009:adverse effects*; D015551:Autoimmunity; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007592:Joint Diseases / Q000139:chemically induced*; D008875:Middle Aged; D009135:Muscular Diseases / Q000139:chemically induced*; D009367:Neoplasm Staging; D011446:Prospective Studies
chemical_list: D047072:Aromatase Inhibitors