title: Prognostic significance of tumor cell proliferation analyzed in fine needle aspirates from primary breast cancer.
abstract: 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 > or = 15% (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 >20 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 > or = 15%. This difference was statistically significant (p < 0.01). For patients with tumors <20mm 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 > or = 15% (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.
authors.affiliation: Department of Oncology and Pathology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden. a.billgren@telia.com
authors.forename: A M
authors.initials: AM
authors.lastname: Billgren
authors.forename: E
authors.initials: E
authors.lastname: Tani
authors.forename: A
authors.initials: A
authors.lastname: Liedberg
authors.forename: L
authors.initials: L
authors.lastname: Skoog
authors.forename: L E
authors.initials: LE
authors.lastname: Rutqvist
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D002455:Cell Division / Q000502:physiology*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone