title: Serial plasma osteopontin levels have prognostic value in metastatic breast cancer.
abstract: OBJECTIVE
  Osteopontin is a malignancy-associated protein measurable in blood and tumor tissue. To evaluate its prognostic value in advanced disease, we conducted a prospective clinical study measuring serial osteopontin plasma levels in women with metastatic breast cancer throughout the course of their disease.
  
  
  METHODS
  One hundred fifty-eight women with newly diagnosed metastatic breast cancer were enrolled in the study. Plasma osteopontin was measured using our validated ELISA, at baseline and every 3 to 12 weeks during and after therapy until death. Multivariate time-dependent survival analyses were conducted using models that right censored patient outcomes 3, 6, and 12 months after the last known osteopontin measurement.
  
  
  RESULTS
  Osteopontin was measured in 1,378 samples (median, 9 per patient). Ninety-nine patients had elevated baseline osteopontin (median, 177 ng/mL; range, 1-2,648 ng/mL). In univariate analysis, elevated baseline osteopontin was associated with short survival (P = 0.02). In a multivariate model incorporating standard prognostic factors, baseline osteopontin was significantly associated with survival duration (relative risk, 1.001; P = 0.038). Metastasis-free interval, visceral metastases, and Eastern Cooperative Oncology Group status 2 to 4 also retained significance. In a multivariate model incorporating standard prognostic factors and changes in sequential osteopontin levels, an osteopontin increase of >250 ng/mL at any time was the variable with the most prognostic value for poor survival (relative risk, 3.26; P = 0.0003), and poor Eastern Cooperative Oncology Group status also retained significance.
  
  
  CONCLUSIONS
  This is the first study to show that in women with metastatic breast cancer, increases in osteopontin levels over time are strongly associated with poor survival. Sequential monitoring of osteopontin may have use in making treatment decisions for these patients.
authors.affiliation: Tom Baker Cancer Centre, Calgary, Alberta, Canada. vivienbr@cancerboard.ab.ca
authors.forename: Vivien H C
authors.initials: VH
authors.lastname: Bramwell
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Doig
authors.forename: Alan B
authors.initials: AB
authors.lastname: Tuck
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Wilson
authors.forename: Katia S
authors.initials: KS
authors.lastname: Tonkin
authors.forename: Anna
authors.initials: A
authors.lastname: Tomiak
authors.forename: Francisco
authors.initials: F
authors.lastname: Perera
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Vandenberg
authors.forename: Ann F
authors.initials: AF
authors.lastname: Chambers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000556:secondary* / Q000628:therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D053495:Osteopontin / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D053495:Osteopontin