title: In vitro DNA synthesis in freshly separated human breast cancer cells assessed by tritiated thymidine incorporation assay: relationship to the long-term outcome of patients.
abstract: BACKGROUND
  Tumour growth rate has a significant effect on the clinical course of various malignancies. The present study was designed to assess whether in vitro DNA synthesis in freshly separated breast cancer cells is a useful marker in evaluating growth rates and in predicting the clinical outcome of patients.
  
  
  METHODS
  From 1982 to 1992, DNA synthesis was assessed by [3H]thymidine incorporation in 97 samples of primary lesions from 94 patients with breast cancer. The patients were followed for 5-15 years and their outcome was surveyed in January 1998.
  
  
  RESULTS
  The level of DNA synthesis did not correlate with the patients' age, clinical stage or expression of oestrogen receptor. However, it correlated significantly with the histological grade. In 89 patients, whose outcome was reported, the survival rate in the group with a high rate of DNA synthesis (log10c.p.m. 3.0 or more) was significantly lower than that in the low-level group; the 5- and 10-year survival rates were 84 and 74 per cent for the low synthesis group (n = 46), and 60 and 46 per cent for the high synthesis group (n = 43) respectively. This was also noted in patients with stage 1 or 2 cancers, for whom the 5- and 10-year survival rates were 100 and 90 per cent for the low synthesis group (n = 25), and 75 and 70 per cent for the high synthesis group (n= 35). Multivariate analysis supported this significant correlation for DNA synthesis in the prognosis of patients after mastectomy. Furthermore, the level of DNA synthesis was significantly higher in 18 patients who died from a recurrence within 3 years after operation than in 56 survivors, and the level of DNA synthesis also correlated significantly with the survival period in the 33 patients who died.
  
  
  CONCLUSIONS
  The level of DNA synthesis in breast cancer was variable, and was independent of the clinical stage or oestrogen receptor status. However, a high level of DNA synthesis was a positive indicator of a high risk of recurrence after operation, especially for stage 1 or 2 breast cancer. In vitro DNA synthesis may account for some of the clinical characteristics of breast cancers.
authors.affiliation: First Department of Surgery, Shimane Medical University, Izumo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nio
authors.forename: K
authors.initials: K
authors.lastname: Tamura
authors.forename: N
authors.initials: N
authors.lastname: Kan
authors.forename: T
authors.initials: T
authors.lastname: Inamoto
authors.forename: K
authors.initials: K
authors.lastname: Ohgaki
authors.forename: H
authors.initials: H
authors.lastname: Kodama
mesh_terms: D000704:Analysis of Variance; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D012307:Risk Factors; D013936:Thymidine; D014407:Tumor Cells, Cultured / Q000378:metabolism*
chemical_list: D004273:DNA, Neoplasm; D013936:Thymidine