title: Adjuvant sequencing of tamoxifen and anastrozole is superior to tamoxifen alone in postmenopausal women with low proliferating breast cancer.
abstract: OBJECTIVE
  To assess the predictive value of Ki67 expression in postmenopausal hormone receptor-positive early-breast cancer patients, who were either treated with adjuvant tamoxifen (TAM) alone or with TAM followed by anastrozole (ANA).
  
  
  METHODS
  Expression of Ki67 was determined centrally by immunohistochemistry on whole tissue sections of postmenopausal endocrine-responsive breast cancers from patients who had been enrolled in the prospectively randomized Austrian Breast and Colorectal Cancer Study Group Trial 8, and had received TAM for 5 years, or TAM for 2 years followed by ANA for 3 years. Ki67 expression was evaluated both as a continuous variable and dichotomized to low (≤10%) and high (>10%). Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox models adjusted for clinical and pathologic parameters.
  
  
  RESULTS
  Patients with a high Ki67 expression (394/1,587; 23%) had a significantly shorter RFS (adjusted HR for recurrence = 1.90, 95% CI: 1.37-2.64, P = 0.0001) and OS (adjusted HR for death = 1.78, 95% CI: 1.18-2.70, P = 0.006). In women with breast tumors expressing medium or high ER levels (n = 1,438), the interaction between Ki67 and adjuvant endocrine treatment was significant for RFS (P = 0.03). TAM followed by ANA was superior to TAM alone in patients with low Ki67 (adjusted HR = 0.53, 95% CI: 0.34-0.83, P = 0.005) but not in high Ki67 disease (adjusted HR = 1.18, 95% CI: 0.66-1.89, P = 0.68).
  
  
  CONCLUSIONS
  Adjuvant sequencing of TAM and ANA is superior to TAM alone, particularly in postmenopausal women with medium or high ER expressing, low proliferating breast cancer.
authors: Departments of Pathology, Surgery, Special Gynecology, and Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors: Zsuzsanna
authors: Z
authors: Bago-Horvath
authors: Margaretha
authors: M
authors: Rudas
authors: Peter
authors: P
authors: Dubsky
authors: Raimund
authors: R
authors: Jakesz
authors: Christian F
authors: CF
authors: Singer
authors: Ralf
authors: R
authors: Kemmerling
authors: Richard
authors: R
authors: Greil
authors: Andrea
authors: A
authors: Jelen
authors: Gerhard
authors: G
authors: Böhm
authors: Zerina
authors: Z
authors: Jasarevic
authors: Anton
authors: A
authors: Haid
authors: Christine
authors: C
authors: Gruber
authors: Sabine
authors: S
authors: Pöstlberger
authors: Martin
authors: M
authors: Filipits
authors: Michael
authors: M
authors: Gnant
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D017024:Chemotherapy, Adjuvant / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use*; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D017698:Postmenopause; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use*; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019394:Ki-67 Antigen; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole