title: Prognostic markers in node-negative breast cancer: a prospective study.
abstract: BACKGROUND
  Despite years of research, it is still unclear which women with node-negative (N-) breast cancer will need adjuvant chemotherapy and which women are being treated unnecessarily. Our goal was to determine which factors best predicted disease free survival (DFS) or cancer-specific overall survival (OS) and, therefore, select the correct patients for treatment. A total of 11 parameters were measured: estrogen receptor (ER), progesterone receptor (PR), age, race, ploidy status, %G0/G1 (% non-DNA synthesis), %S (% S-phase), cathepsin D status, size, stage, and histologic grade.
  
  
  RESULTS
  In this prospective study, we followed 556 N- patients diagnosed between 1991 and 1996. The tumors were 56% ER+, 51% PR+, 30% diploid, with a mean %S of 8.9%. The level of cathepsin D ranged from 0.50 to 155 pmol/mg of protein with a mean of 42.9 pmol/mg of protein. There were 87 recurrences (16%) and 72 cancer deaths (13%), with a median follow-up of 7.8 years. Ploidy status (p = 0.01), S-phase activity (p = 0.003), G1 phase activity (p = 0.02) and age (p = 0.01) were able to significantly predict DFS in a univariate manner. All of the measurable factors were significant or borderline significant in predicting OS in a univariate manner except for age, race, and ER status. In multivariate analysis with S-phase included, it was the only remaining factor in DFS and OS; with S-phase excluded, age and ploidy status remained as factors for DFS in stepwise regression, while PR, size, and cathepsin D were the remaining factors that predicted cancer-specific OS. The effect of adjuvant treatment on prognosis was also analyzed.
  
  
  CONCLUSIONS
  Both biochemical and clinical parameters have the potential to predict prognosis for N- breast cancer. In this large prospective clinical trial, with a median follow-up of 7.8 years, no individual marker adequately predicted the prognosis for an individual patient. %S activity was the best independent marker, but only 77% of the tumors provided this value. Subset analysis provided improved prognostication, but there were limits to its utility. These data represents a definitive study starting in 1991 and ending in 2002.
authors.affiliation: Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1072, USA. tkute@wfubmc.edu
authors.forename: T E
authors.initials: TE
authors.lastname: Kute
authors.forename: G B
authors.initials: GB
authors.lastname: Russell
authors.forename: N
authors.initials: N
authors.lastname: Zbieranski
authors.forename: R
authors.initials: R
authors.lastname: Long
authors.forename: S
authors.initials: S
authors.lastname: Johnston
authors.forename: H
authors.initials: H
authors.lastname: Williams
authors.forename: C
authors.initials: C
authors.lastname: Stackhouse
authors.forename: L
authors.initials: L
authors.lastname: Wilkins
authors.forename: I
authors.initials: I
authors.lastname: Evans
authors.forename: P
authors.initials: P
authors.lastname: Berry
authors.forename: K
authors.initials: K
authors.lastname: Rimmer
authors.forename: E
authors.initials: E
authors.lastname: Tucker
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D056649:Cathepsin G; D002403:Cathepsins / Q000032:analysis*; D002453:Cell Cycle; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D011003:Ploidies; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012697:Serine Endopeptidases
chemical_list: D014408:Biomarkers, Tumor; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G