Clinical significance of proliferative activity evaluated by MIB-1 in the treatment and postoperative follow-up of early breast cancer

Abstract

21054 Background: To evaluate a clinical significance of proliferative activity in breast cancer, we studied relationships between proliferative activity and recurrence rate, the time of recurrence or adjuvant therapy. Methods: We analyzed 2448 patients with primary breast cancer between 1987 and 2004 in the Kumamoto City Hospital, and 437 cases out of the patients developed recurrence. Furthermore, the rate of recurrence before and after 1999 when postoperative adjuvant therapy (such as CEF or Taxanes) was started as standard treatment was investigated. Proliferative activity was judged by immunostaining for MIB-1. The fraction of proliferating cells was classified into 3 degrees (=19%, 20–49%, 50%=). Median observation period was 70 months. Results: 1) Distribution of patients by proliferation was as follows; =19%:1215 cases(50%), 20–49%: 870 cases(35%), or 50%=: 363 cases(15%). There was a significant relationship between proliferative activity and tumor size, nodal status, ER, PgR, p53 or HER2 status. 2) Multivariate analysis for disease-free survival revealed that a proliferative activity was one of significant factors in node-negative and positive cases. Recurrence rate was 11.6% in cases with low proliferation and 31.0% in high proliferation. The mean period from operation to recurrence in cases with low proliferation was 50.2 months, whereas 19.9 months in high proliferation (p<0.0001). Moreover, 74% of recurrent cases with high proliferation recurred within 2 years after operation, and there were few recurrences from the fifth year. 3) Patients with low proliferation frequently developed bone metastasis. In local recurrence, diffuse skin recurrence was often seen in cases with high proliferation. 4) The prognosis of patients in the later period (standard therapy group) was significantly better than that of patients in the earlier period, especially in high proliferation group. Conclusions: Proliferative activity might reflect aggressive behavior of breast cancer and predict the time of recurrence. The standard adjuvant therapy was effective in inhibiting early recurrence with high proliferation. It is important to take proliferative activity into consideration in the treatment and follow-up of breast cancer. No significant financial relationships to disclose.