Prognostic significance of tumor cell proliferation analyzed in fine needle aspirates from primary breast cancer

The objective of this study was to analyze the role of proliferating fraction (PF) measured with Ki-67/MIB-1 antibody in a large series of preoperative fine-needle aspirate (FNA) biopsies as a prognosticator of disease recurrence. The study comprised 732 patients who all had a conclusive cytological diagnosis of breast cancer. The follow-up time ranged from 1.2 to 10.2 years with a median of 5.7 years. In multivariate analysis Ki-67/MIB-1 value was a strong (p < 0.001) significant, prognosticator of disease recurrence free interval (DRFI) independent of lymph node status, progesterone receptor content, and tumor size. In the subgroup analysis of 430 node-negative patients the distant recurrence-free rate after 5 years was 94.4% in patients with Ki-67/MIB-1 value < 15% compared to 88.7% in patients with Ki-67/MIB-1 value greater than or equal to15% (p = 0.03). Test of the interaction between tumor size and the value of PF revealed a p-value of 0.06. If the patients, in addition, had a tumor size greater than or equal to20 mm the distant recurrence-free rate after 5 years was 93.2% if Ki-67/MIB-1 < 15% compared to 80.7% in patients with Ki-67/MIB-1 value greater than or equal to15%. This difference was statistically significant (p < 0.01). For patients with tumors <20 mm Ki-67/MIB-1 value did not add any prognostic information. In the subgroup of 302 node-positive patients the distant recurrence-free rate after 5 years was 86.0% in patients with Ki-67/MIB-1 value < 15% compared to 70.6% in patients with Ki-67/MIB-1 value greater than or equal to15% (p < 0.01). We conclude that PF assessed by Ki-67/MIB-1 antibodies in preoperative FNA biopsies has a significant prognostic value independent of lymph node status, PgR status and tumor size. To our knowledge, this is the first study demonstrating PF, which can contribute prognostic information when analyzed in preoperative smears.