title: Women commencing anastrozole, letrozole or tamoxifen for early breast cancer: the impact of comorbidity and demographics on initial choice.
abstract: BACKGROUND
  Australian clinical guidelines recommend endocrine therapy for all women with hormone-dependent early breast cancer. Guidelines specify tamoxifen as first-line therapy for pre-menopausal women, and tamoxifen or an aromatase inhibitor (AI) for post-menopausal women depending on the risk of recurrence based on tumour characteristics including size. Therapies have different side effect profiles; therefore comorbidity may also influence choice. We examined comorbidity, and the clinical and demographic characteristics of women commencing different therapies.
  
  
  METHODS
  We identified the first dispensing of tamoxifen, anastrozole or letrozole for women diagnosed with invasive breast cancer in the 45 and Up Study from 2004-2009 (N = 1266). Unit-level pharmacy and medical service claims, hospital, Cancer Registry, and self-reported data were linked to determine menopause status at diagnosis, tumour size, age, comorbidities, and change in subsidy restrictions. Chi-square tests and generalised regression models were used to compare the characteristics of women commencing different therapies.
  
  
  RESULTS
  Most pre-menopausal women commenced therapy with tamoxifen (91%). Anastrozole was the predominant therapy for post-menopausal women (57%), followed by tamoxifen (28%). Women with osteoporosis were less likely to commence anastrozole compared with tamoxifen (anastrozole RR = 0.7, 95% CI = 0.5-0.9). Women with arthritis were 1.6-times more likely to commence letrozole than anastrozole (95% CI = 1.1-2.1). Tamoxifen was more often initiated in women with tumours >1 cm, who were also ≥75 years. Subsidy restriction changes were associated with substantial increases in the proportion of women commencing AIs (anastrozole RR = 4.3, letrozole RR = 8.3).
  
  
  CONCLUSIONS
  The findings indicate interplay of comorbidity and therapy choice for women with invasive breast cancer. Most post-menopausal women commenced therapy with anastrozole; however, letrozole and tamoxifen were more often initiated for women with comorbid arthritis and osteoporosis, respectively. Tamoxifen was also more common for women with tumours >1 cm and aged ≥75 years. Subsidy restrictions appear to have strongly influenced therapy choice.
authors.affiliation: Centre for Health Services Research, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: Kemp
authors.affiliation: Centre for Health Services Research, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: David B
authors.initials: DB
authors.lastname: Preen
authors.affiliation: School of Surgery, The University of Western Australia, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Christobel
authors.initials: C
authors.lastname: Saunders
authors.affiliation: Patricia Richie Centre for Cancer Care and Research, The Mater Hospital, Sydney, New South Wales, Australia.
authors.forename: Frances
authors.initials: F
authors.lastname: Boyle
authors.affiliation: Institute of Health Research, University of Notre Dame, Perth, Western Australia, Australia.
authors.forename: Max
authors.initials: M
authors.lastname: Bulsara
authors.affiliation: Centre for Health Services Research, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: C D'Arcy J
authors.initials: CD
authors.lastname: Holman
authors.affiliation: Centre for Health Services Research, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Eva
authors.initials: E
authors.lastname: Malacova
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Roughead
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001315:Australia; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009367:Neoplasm Staging; D009570:Nitriles / Q000627:therapeutic use*; D017698:Postmenopause; D017410:Practice Guidelines as Topic; D017697:Premenopause; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D013629:Tamoxifen / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*; D047368:Tumor Burden
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D009570:Nitriles; D020845:Selective Estrogen Receptor Modulators; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole; D000077289:Letrozole