title: Early discontinuation of endocrine therapy for breast cancer: who is at risk in clinical practice?
abstract: OBJECTIVE
  Despite evidence supporting at least five years of endocrine therapy for early breast cancer, many women discontinue therapy early. We investigated the impact of initial therapy type and specific comorbidities on discontinuation of endocrine therapy in clinical practice.
  
  
  METHODS
  We identified women in a population-based cohort with a diagnosis of early breast cancer and an incident dispensing of anastrozole, letrozole or tamoxifen from 2003-2008 (N = 1531). Pharmacy and health service data were used to determine therapy duration, treatment for pre-existing and post-initiation comorbidities (anxiety, depression, hot flashes, musculoskeletal pain, osteoporosis, vaginal atrophy), demographic and other clinical characteristics. Time to discontinuation of initial, and any, endocrine therapy was calculated. Cox regression determined the association of different characteristics on early discontinuation.
  
  
  RESULTS
  Initial endocrine therapy continued for a median of 2.2 years and any endocrine therapy for 4.8 years. Cumulative probability of discontinuing any therapy was 17% after one year and 58% by five years. Initial tamoxifen, pre-existing musculoskeletal pain and newly-treated anxiety predicted shorter initial therapy but not discontinuation of any therapy. Early discontinuation of any therapy was associated with newly-treated hot flashes (HR = 2.1, 95% CI = 1.3-3.3), not undergoing chemotherapy (HR = 1.4, 95% CI = 1.1-1.8) and not undergoing mastectomy (HR = 1.5, 95% CI = 1.2-1.8).
  
  
  CONCLUSIONS
  Less than half of women completed five years of endocrine therapy. Women at greatest risk of stopping any therapy early were those with newly-treated hot flashes, no initial chemotherapy, or no initial mastectomy. This suboptimal use means that the reductions in recurrence demonstrated in clinical trials may not be realised in practice.
authors.affiliation: Centre for Health Services Research, School of Population Health, The University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009 Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: Kemp
authors.affiliation: Centre for Health Services Research, School of Population Health, The University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009 Australia.
authors.forename: David B
authors.initials: DB
authors.lastname: Preen
authors.affiliation: School of Surgery, The University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009 Australia.
authors.forename: Christobel
authors.initials: C
authors.lastname: Saunders
authors.affiliation: Patricia Richie Centre for Cancer Care and Research, The Mater Hospital, University of Sydney, Rocklands Road, North Sydney, NSW 2060 Australia.
authors.forename: Frances
authors.initials: F
authors.lastname: Boyle
authors.affiliation: Institute of Health and Rehabilitation Research, University of Notre Dame, PO Box 1225, Fremantle, WA 6959 Australia.
authors.forename: Max
authors.initials: M
authors.lastname: Bulsara
authors.affiliation: Centre for Health Services Research, School of Population Health, The University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009 Australia.
authors.forename: Eva
authors.initials: E
authors.lastname: Malacova
authors.affiliation: Quality Use of Medicines and Pharmacy Research Centre, School of Pharmacy and Medical Sciences, University of South Australia, GPO Box 2471, Adelaide, SA 5001 Australia.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Roughead
keywords: 45 and up study; Adherence; Aromatase inhibitors; Persistence; Tamoxifen