title: Effects of adjuvant exemestane versus anastrozole on bone mineral density for women with early breast cancer (MA.27B): a companion analysis of a randomised controlled trial.
abstract: BACKGROUND
  Treatment of breast cancer with aromatase inhibitors is associated with damage to bones. NCIC CTG MA.27 was an open-label, phase 3, randomised controlled trial in which women with breast cancer were assigned to one of two adjuvant oral aromatase inhibitors-exemestane or anastrozole. We postulated that exemestane-a mildly androgenic steroid-might have a less detrimental effect on bone than non-steroidal anastrozole. In this companion study to MA.27, we compared changes in bone mineral density (BMD) in the lumbar spine and total hip between patients treated with exemestane and patients treated with anastrozole.
  
  
  METHODS
  In MA.27, postmenopausal women with early stage hormone (oestrogen) receptor-positive invasive breast cancer were randomly assigned to exemestane 25 mg versus anastrozole 1 mg, daily. MA.27B recruited two groups of women from MA.27: those with BMD T-scores of -2·0 or more (up to 2 SDs below sex-matched, young adult mean) and those with at least one T-score (hip or spine) less than -2·0. Both groups received vitamin D and calcium; those with baseline T-scores of less than -2·0 also received bisphosphonates. The primary endpoints were percent change of BMD at 2 years in lumbar spine and total hip for both groups. We analysed patients according to which aromatase inhibitor and T-score groups they were allocated to but BMD assessments ceased if patients deviated from protocol. This study is registered with ClinicalTrials.gov, NCT00354302.
  
  
  RESULTS
  Between April 24, 2006, and May 30, 2008, 300 patients with baseline T-scores of -2·0 or more were accrued (147 allocated exemestane, 153 anastrozole); and 197 patients with baseline T-scores of less than -2·0 (101 exemestane, 96 anastrozole). For patients with T-scores greater than -2·0 at baseline, mean change of bone mineral density in the spine at 2 years did not differ significantly between patients taking exemestane and patients taking anastrozole (-0·92%, 95% CI -2·35 to 0·50 vs -2·39%, 95% CI -3·77 to -1·01; p=0·08). Respective mean loss in the hip was -1·93% (95% CI -2·93 to -0·93) versus -2·71% (95% CI -4·32 to -1·11; p=0·10). Likewise for those who started with T-scores of less than -2·0, mean change of spine bone mineral density at 2 years did not differ significantly between the exemestane and anastrozole treatment groups (2·11%, 95% CI -0·84 to 5·06 vs 3·72%, 95% CI 1·54 to 5·89; p=0·26), nor did hip bone mineral density (2·09%, 95% CI -1·45 to 5·63 vs 0·0%, 95% CI -3·67 to 3·66; p=0·28). Patients with baseline T-score of -2·0 or more taking exemestane had two fragility fractures and two other fractures, those taking anastrozole had three fragility fractures and five other fractures. For patients who had baseline T-scores of less than -2·0 taking exemestane, one had a fragility fracture and four had other fractures, whereas those taking anastrozole had five fragility fractures and one other fracture.
  
  
  CONCLUSIONS
  Our results demonstrate that adjuvant treatment with aromatase inhibitors can be considered for breast cancer patients who have T-scores less than -2·0.
  
  
  BACKGROUND
  Canadian Cancer Society Research Institute, Pfizer, Canadian Institutes of Health Research.
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA. Electronic address: pgoss@partners.org.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Goss
authors.affiliation: Columbia University Medical Center, New York, NY, USA.
authors.forename: Dawn L
authors.initials: DL
authors.lastname: Hershman
authors.affiliation: University of Toronto, Toronto, ON, Canada.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Cheung
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Sundeep
authors.initials: S
authors.lastname: Khosla
authors.affiliation: Johns Hopkins Oncology Centre, School of Medicine, Baltimore, MD, USA.
authors.forename: Vered
authors.initials: V
authors.lastname: Stearns
authors.affiliation: Allan Blair Cancer Centre, Regina, SK, Canada.
authors.forename: Haji
authors.initials: H
authors.lastname: Chalchal
authors.affiliation: Carle CCOP, Urbana-Champaign, IL, USA.
authors.forename: Kendrith
authors.initials: K
authors.lastname: Rowland
authors.affiliation: University of North Carolina/Lineberger Comp Cancer Center, Chapel Hill, NC, USA.
authors.forename: Hyman B
authors.initials: HB
authors.lastname: Muss
authors.affiliation: University of Washington, Seattle, WA, USA.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Linden
authors.affiliation: University of Toronto, Toronto, ON, Canada.
authors.forename: Judite
authors.initials: J
authors.lastname: Scher
authors.affiliation: Sunnybrook Odette Cancer Centre, Toronto, ON, Canada.
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.affiliation: NCIC Clinical Trials Group, Queen's University, Kingston, ON, Canada.
authors.forename: Catherine R
authors.initials: CR
authors.lastname: Elliott
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Tanja
authors.initials: T
authors.lastname: Badovinac-Crnjevic
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: St Louis
authors.affiliation: NCIC Clinical Trials Group, Queen's University, Kingston, ON, Canada.
authors.forename: Judith-Anne W
authors.initials: JA
authors.lastname: Chapman
authors.affiliation: NCIC Clinical Trials Group, Queen's University, Kingston, ON, Canada.
authors.forename: Lois E
authors.initials: LE
authors.lastname: Shepherd
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D050281:Bones of Lower Extremity / Q000000981:diagnostic imaging / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002118:Calcium / Q000627:therapeutic use; D002170:Canada; D017024:Chemotherapy, Adjuvant; D019587:Dietary Supplements; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D017698:Postmenopause; D011859:Radiography; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*; D014481:United States; D014807:Vitamin D / Q000627:therapeutic use
chemical_list: D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D009570:Nitriles; D014230:Triazoles; D014807:Vitamin D; D000077384:Anastrozole; C056516:exemestane; D002118:Calcium