Abstract P6-06-10: Prognostic role of Ki67 determined on metastatic biopsies in patients with advanced breast cancer
Authors: Falato C , Lorent J , Kessler L , Karlsson E , Wilking U , Wright P , Skoog L , Bergh J , Foukakis T 
Published: August 2014

Background: The value of proliferation as a biomarker has been extensively investigated in early breast cancer. On the contrary, its role in advanced setting is currently unexplored. The aim of our study was to determine the prognostic value of Ki67 evaluated at the time of first systemic relapse (mKi67) in patients with metastatic breast cancer (MBC).

Patients and Methods: Two hundred ten patients diagnosed and treated for MBC in Stockholm between 1998 and 2009 and for whom mKi67 was available, were retrospectively identified using the regional, population-based, cancer registry. mKi67 had been analyzed on fine needle or core biopsies using standard assays at the routine pathology lab. The bone was the most common site of biopsy (n = 58), followed by the liver (n = 49). Patients were divided into two groups according to the levels of mKi67 (high &gt;20% or low ≤ 20%). Overall survival (OS) from the time of first distant recurrence was compared between the groups using the Kaplan-Meier and Cox regression methods. The effect of age at relapse, recurrence-free interval, (neo-) adjuvant chemotherapy as well as axillary lymph nodes status, estrogen receptor status and Ki67 of the primary tumor (pKi67) was evaluated using Cox analysis. In a multivariate model, stratified by the period of primary tumor diagnosis, only the variables significantly associated with OS in univariate analysis were included. Further, the prognostic value of mKi67 as continuous variable was evaluated. The intra-individual change in Ki67 expression levels between primary tumor and metastasis was investigated using the McNemar's test and its prognostic value was explored by Kaplan-Meier plots.

Results: 125 patients had low and 85 had high mKi67 levels. After a median follow-up of 115 months (95% CI = 104-126), 186 events were registered, 109 in the low- mKi67 and 77 in the high- mKi67 group. Median OS after relapse was 25 and 17 months in low- and high- mKi67 group respectively (HR = 0.69, 95% CI = 0.51- 0.92, p = 0.01 by log-rank test). Further, 2-year estimated OS rate decreased steeply as the mKi67 levels increased. Only axillary lymph node status showed an independent prognostic value (HR = 0.65, 95% CI = 0.47- 0.90, p = 0.0095) in the multivariate analysis. pKi67 was available in 131 patients. Ki67 changed from primary tumor to relapse in 41,2% of the cases, from low to high in 13.7% and from high to low in 27,5% (p = 0.02). Exploratory survival plots did not indicate an effect of change in Ki67 on OS. In a regression model including only mKi67 and pKi67 as covariates, mKi67 showed an independent association with OS (HR = 0.67, 95%CI = 0.50-0.91, p = 0.0091).

Conclusions: In this cohort of patients with MBC, Ki67 determined on metastatic biopsies is inversely associated with survival, independently from the proliferation of the primary tumor. Proliferation levels change significantly during tumor progression.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-10.