Introduction: The Ki-67 index value is a prognostic factor in primary breast cancer and is a proliferation marker that also distinguishes between luminal type A and type B breast cancer. Moreover, change in Ki-67 index value due to treatment and recurrence is considered to be important in treating breast cancer. The evaluative procedure in this study was on two levels; first, we examined whether the baseline Ki-67 value at the primary tumor is useful as a prognostic factor after recurrence, and second, we looked at the changes in the values after recurrence.

Patients and Methods: Immunohistochemical (IHC) analysis of the Ki-67 index was performed on 4701 patients with primary breast cancer from 1987 until March 2013 at Kumamoto City Hospital. Out of these patients, there were 666 consecutive cases with recurrence after primary surgery. The fraction of proliferating cells (positive for Ki-67) was based on a count of at least 500 tumor cells in the area including the hot spot, and the Ki-67 values were divided into 2 or 3 groups; <20% and ≥20% (and ≥50%). Items examined were ER, PgR, HER2, tumor size, nodal status at primary tumor, and recurrent site (soft tissue, bone and viscera) and disease-free interval (DFI). Cox's proportional hazard model was used to perform a univariate and multivariate analyses of the factors related to overall survival (OS) after recurrence. The median follow-up period was 65.9 months in the remaining survival group. In 101 recurrent cases from whom the recurrent lesion was resected, the change in biological markers (Ki-67, ER and PgR) were evaluated.

Results: The median Ki-67 value at baseline was 20% in all the cases and 27% in the recurrent cases. In terms of recurrent site, the values were low (23%) in patients with bone metastasis, whereas patients with liver or brain metastasis showed higher values (38% and 53%, respectively). Moreover, DFI was inversely correlated with Ki-67 values. Univariate and multivariate analyses were performed to identify the prognostic factors for OS after recurrence. The significant factors included tumor size, lymph node status, ER, PgR, DFI, recurrent site, and the Ki-67 index value. Among these factors, a multivariate analysis revealed that the Ki-67 index value at primary tumor was an independent significant factor. The hormone receptor positive rate from the primary tumor to recurrence decreased from 67.3% to 63.4% and 64.4% to 50% for ER and PgR, respectively. The Ki-67 index value increased significantly from a mean of 28.9% at primary tumor to 35.7% at relapse. Furthermore, the Ki-67 index value at primary tumor was a significant prognostic factor for OS after recurrence in this cohort.

Conclusion: The Ki-67 value at primary tumor was a significant prognostic factor for OS after recurrence. The Ki-67 index value increased significantly after recurrence. It is therefore important to take the Ki-67 index into consideration in the treatment and follow-up of breast cancer patients.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-14.