title: CA15-3 and alkaline phosphatase as predictors for breast cancer recurrence: a combined analysis of seven International Breast Cancer Study Group trials.
abstract: BACKGROUND
  We evaluated the ability of CA15-3 and alkaline phosphatase (ALP) to predict breast cancer recurrence.
  
  
  METHODS
  Data from seven International Breast Cancer Study Group trials were combined. The primary end point was relapse-free survival (RFS) (time from randomization to first breast cancer recurrence), and analyses included 3953 patients with one or more CA15-3 and ALP measurement during their RFS period. CA15-3 was considered abnormal if >30 U/ml or >50% higher than the first value recorded; ALP was recorded as normal, abnormal, or equivocal. Cox proportional hazards models with a time-varying indicator for abnormal CA15-3 and/or ALP were utilized.
  
  
  RESULTS
  Overall, 784 patients (20%) had a recurrence, before which 274 (35%) had one or more abnormal CA15-3 and 35 (4%) had one or more abnormal ALP. Risk of recurrence increased by 30% for patients with abnormal CA15-3 [hazard ratio (HR) = 1.30; P = 0.0005], and by 4% for those with abnormal ALP (HR = 1.04; P = 0.82). Recurrence risk was greatest for patients with either (HR = 2.40; P < 0.0001) and with both (HR = 4.69; P < 0.0001) biomarkers abnormal. ALP better predicted liver recurrence.
  
  
  CONCLUSIONS
  CA15-3 was better able to predict breast cancer recurrence than ALP, but use of both biomarkers together provided a better early indicator of recurrence. Whether routine use of these biomarkers improves overall survival remains an open question.
authors.affiliation: International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Keshaviah
authors.forename: S
authors.initials: S
authors.lastname: Dellapasqua
authors.forename: N
authors.initials: N
authors.lastname: Rotmensz
authors.forename: J
authors.initials: J
authors.lastname: Lindtner
authors.forename: D
authors.initials: D
authors.lastname: Crivellari
authors.forename: J
authors.initials: J
authors.lastname: Collins
authors.forename: M
authors.initials: M
authors.lastname: Colleoni
authors.forename: B
authors.initials: B
authors.lastname: Thürlimann
authors.forename: C
authors.initials: C
authors.lastname: Mendiola
authors.forename: S
authors.initials: S
authors.lastname: Aebi
authors.forename: K N
authors.initials: KN
authors.lastname: Price
authors.forename: O
authors.initials: O
authors.lastname: Pagani
authors.forename: E
authors.initials: E
authors.lastname: Simoncini
authors.forename: M
authors.initials: M
authors.lastname: Castiglione Gertsch
authors.forename: R D
authors.initials: RD
authors.lastname: Gelber
authors.forename: A S
authors.initials: AS
authors.lastname: Coates
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D018396:Mucin-1 / Q000097:blood*; D009364:Neoplasm Recurrence, Local; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D018396:Mucin-1; D000469:Alkaline Phosphatase