title: Randomized trial of tamoxifen versus combined tamoxifen and octreotide LAR Therapy in the adjuvant treatment of early-stage breast cancer in postmenopausal women: NCIC CTG MA.14.
abstract: OBJECTIVE
  Somatostatin analogs act directly on breast cancer cells and indirectly on insulin and insulin-like growth factor 1 (IGF-1) levels. This trial was undertaken to assess whether octreotide would lower insulin and IGF-1 levels and reduce risk of breast cancer recurrence.
  
  
  METHODS
  The NCIC CTG MA.14 (NCIC Clinical Trials Group MA.14) trial randomly assigned postmenopausal women to 5 years of tamoxifen 20 mg daily (TAM) or TAM plus 2 years of octreotide 90 mg depot intramuscular injections monthly (TAM-OCT) as adjuvant therapy. The primary end point was event-free survival (EFS). Secondary end points were relapse-free survival (RFS), overall survival (OS), toxicity, and effects of treatment on IGF physiology.
  
  
  RESULTS
  Among 667 women with a median follow-up of 7.9 years, 220 events occurred-108 with TAM-OCT and 112 with TAM. Adjusted hazard ratios (HRs; TAM-OCT to TAM) were 0.93 for EFS (95% CI, 0.71 to 1.22; P = .62), 0.84 for RFS (95% CI, 0.59 to 1.18; P = .31), and 0.97 for OS (95% CI, 0.69 to 1.37; P = .86). Among patients with normal baseline gallbladder imaging, cholecystectomy was required in 23.0% of those receiving TAM-OCT but in only 1.4% of those receiving TAM (P < .001). At 4 months, TAM-OCT had significantly (P < .001) lowered IGF-1, IGF binding protein 3, and C-peptide levels. Older age (P = .02), tumor size (P = .001), nodal status (P = .01), high C-peptide levels (P < .001), and higher body mass index (BMI) in models excluding C-peptide (P < .001) were associated with poorer EFS in multivariate analysis.
  
  
  CONCLUSIONS
  Octreotide-related changes in circulating IGF-1 and C-peptide levels were statistically significant. Octreotide did not add significant clinical benefit. High C-peptide levels (surrogate for insulin secretion rate) and high BMI were associated with poor outcome.
authors.affiliation: Sunnybrook Odette Cancer Centre and University of Toronto, Toronto, Ontario, Canada. kathy.pritchard@sunnybrook.ca
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.forename: Lois E
authors.initials: LE
authors.lastname: Shepherd
authors.forename: Judith-Anne W
authors.initials: JA
authors.lastname: Chapman
authors.forename: Brian D
authors.initials: BD
authors.lastname: Norris
authors.forename: Jacques
authors.initials: J
authors.lastname: Cantin
authors.forename: Paul E
authors.initials: PE
authors.lastname: Goss
authors.forename: Susan F
authors.initials: SF
authors.lastname: Dent
authors.forename: David
authors.initials: D
authors.lastname: Walde
authors.forename: Ted A
authors.initials: TA
authors.lastname: Vandenberg
authors.forename: Brian
authors.initials: B
authors.lastname: Findlay
authors.forename: Susan E
authors.initials: SE
authors.lastname: O'Reilly
authors.forename: Carolyn F
authors.initials: CF
authors.lastname: Wilson
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.forename: Ettie
authors.initials: E
authors.lastname: Piura
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Whelan
authors.forename: Michael N
authors.initials: MN
authors.lastname: Pollak
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002096:C-Peptide / Q000097:blood; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage / Q000009:adverse effects; D017698:Postmenopause; D011788:Quality of Life; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014807:Vitamin D / Q000097:blood
chemical_list: D018931:Antineoplastic Agents, Hormonal; D002096:C-Peptide; D007328:Insulin; D013629:Tamoxifen; D014807:Vitamin D; D007334:Insulin-Like Growth Factor I; D015282:Octreotide