title: Bone metabolism and quality-of-life of postmenopausal women with invasive breast cancer receiving neoadjuvant hormonal therapy: sub-analyses from celecoxib anti-aromatase neoadjuvant (CAAN) trial.
abstract: OBJECTIVE
  Anti-aromatase therapy is important in the treatment of breast cancer in postmenopausal women but they have effects on the bone mineral density (BMD) and osteoporosis. Cyclooxygenase-2 (COX-2) inhibitors have been shown to be effective in chemoprevention in animal and clinical studies. A proof of principle study was performed to investigate the efficacy of combing anti-aromatase therapy (exemestane) and COX-2 inhibitors neoadjuvantly. The changes in the BMD, bone turnover proteins and quality-of-life (QoL) were analyzed and presented here.
  
  
  METHODS
  82 postmenopausal patients with histologically confirmed invasive hormone-sensitive breast cancers were included for the neoadjuvant therapy (NHT). 30 patients received exemestane (EXE) 25 mg daily and celecoxib (CXB) 400 mg twice daily (group A), 24 patients received EXE 25 mg daily (group B) and 28 patients received letrozole (LET) 2.5 mg daily (group C). The same assigned treatment was intended to continue for 2 years to study the changes in the bone metabolism. BMD of 48 patients were analyzed; 23 belongs to group A, 10 to group B and 15 to group C. The serum bone turnover proteins bone-specific alkaline phosphatase (BAP) and carboxyterminal crosslinked telopeptide of type I collagen (ICTP), were measured with commercially available test kits before treatment, 3 months and 15 months after treatment. Functional Assessment of Cancer Therapy core questionnaire (FACT-G) with its additional breast cancer subscale were performed at baseline, 4, 8, and 12 weeks after NHT.
  
  
  RESULTS
  Difference between groups (p=0.007) for BMD at femur was significant. The changes of BMD in group B patients were significantly greater than patients in group A (p=0.011, CI=0.063-0.437), and group C (p=0.003, CI=0.146-0.620). The mean BAP increased from baseline in group B patients but decreased from baseline in group C patients at 3 months and 15 months. No statistical significance was found in the FACT-G scores and FACT-B scores among different groups at baseline, week 4, week 8 and week 12 after NHT. The Breast Cancer Subscale scores in group A patients were significantly higher than that of group C patients (p=0.021). After 4 weeks of NHT, negative changes of FACT-B and FACT-G scores were found in group B and C patients, but there were positive changes in group A patients. Significant differences of FACT-B score (p=0.008) and FACT-G score (p=0.019) were observed at that time point. Article from the Special issue on Targeted Inhibitors.
authors.affiliation: Clinical Trials Centre, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong. lwcchow@ootr.org
authors.forename: Louis W C
authors.initials: LW
authors.lastname: Chow
authors.forename: Adrian Y S
authors.initials: AY
authors.lastname: Yip
authors.forename: W P
authors.initials: WP
authors.lastname: Chu
authors.forename: Wings T Y
authors.initials: WT
authors.lastname: Loo
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
mesh_terms: D000730:Androstadienes / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy; D017698:Postmenopause; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D011788:Quality of Life; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D015415:Biomarkers; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; C056516:exemestane