title: Comparison of the systemic and intratumoral effects of tamoxifen and the aromatase inhibitor vorozole in postmenopausal patients with primary breast cancer.
abstract: OBJECTIVE
  To determine biologic differences, if any, between presurgical endocrine treatment with an aromatase inhibitor (vorozole) and tamoxifen in patients with postmenopausal primary breast cancer.
  
  
  METHODS
  Randomization was to 12 weeks of 2.5 mg of vorozole per day or 20 mg of tamoxifen per day, both orally. Clinical response was assessed monthly together with serum sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogens (E1, E2, and E1S), lipids, insulin-like growth factor-1 (IGF-1), and bone metabolites (CrossLaps CTx). Tissue samples for Ki67, apoptotic index (AI), estrogen receptor, and progesterone receptor were collected at 0, 2, and 12 weeks.
  
  
  RESULTS
  Ki67 fell by 58% and 43% (means) at 2 weeks in the vorozole and tamoxifen patients, respectively (P =.13). In the vorozole group, the correlations of proportional changes in Ki67 at 2 weeks with tumor volume changes and clinical response at 12 weeks were not significant (P =.09) and marginally significant (P =.04), respectively. Serum lipids did not differ between groups. Serum levels of EI, E2, and E1S were suppressed markedly by vorozole, whereas levels of SHBG increased and LH and FSH fell significantly with tamoxifen. IGF-1 levels fell significantly with tamoxifen (P =.001) compared with the nonsignificant rise with vorozole. Twelve-week CTx values fell by 19% with tamoxifen (P =.006) and rose by 11% with vorozole (P =.15).
  
  
  CONCLUSIONS
  The correlation with vorozole of Ki67 with volume and clinical response supports this as an intermediate marker. The nonsignificant effects on bone and lipid metabolism by the aromatase inhibitor may be important to consider for adjuvant and potential prevention strategies.
authors.affiliation: Department of Biochemistry, Royal Marsden Hospital, London, United Kingdom.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Harper-Wynne
authors.forename: Nigel P M
authors.initials: NP
authors.lastname: Sacks
authors.forename: Karyn
authors.initials: K
authors.lastname: Shenton
authors.forename: Fiona A
authors.initials: FA
authors.lastname: MacNeill
authors.forename: Paul
authors.initials: P
authors.lastname: Sauven
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Laidlaw
authors.forename: Zen
authors.initials: Z
authors.lastname: Rayter
authors.forename: Stephanie
authors.initials: S
authors.lastname: Miall
authors.forename: Angela
authors.initials: A
authors.lastname: Howes
authors.forename: Janine
authors.initials: J
authors.lastname: Salter
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Hills
authors.forename: Frances M
authors.initials: FM
authors.lastname: Lowe
authors.forename: Roger
authors.initials: R
authors.lastname: A'Hern
authors.forename: Nazar
authors.initials: N
authors.lastname: Nasiri
authors.forename: Debbie
authors.initials: D
authors.lastname: Doody
authors.forename: Jhangir
authors.initials: J
authors.lastname: Iqbal
authors.forename: Mitchell
authors.initials: M
authors.lastname: Dowsett
mesh_terms: D000284:Administration, Oral; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000032:analysis; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D007986:Luteinizing Hormone / Q000032:analysis; D008875:Middle Aged; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology*; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles; D013629:Tamoxifen; C060523:vorozole; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone