Clinical Cancer Research, Vol 2, Issue 3 585-592, Copyright © 1996 by American Association for Cancer Research

ARTICLES

Prognostic value of Ki-67 compared to S-phase fraction in axillary node-negative breast cancer

RW Brown, CD Allred, GM Clark, CK Osborne and SG Hilsenbeck
Department of Pathology, The Methodist Hospital, Houston, Texas 77030, USA.

The primary purpose of this study was to evaluate the prognostic significance of Ki-67, a cell proliferation-associated antigen, in a large group (n = 674) of axillary node-negative breast cancer cases with long-term follow-up and to correlate Ki-67 antigen expression with S-phase fraction. Ki-67 immunostaining was assessed both semiquantitatively and quantitatively. The statistical analysis focused on agreement between methods of Ki-67 quantification, agreement between Ki-67 and S-phase fraction, associations between Ki-67 and other clinical variables, and prognostic value of Ki-67. There was excellent agreement between the two methods of Ki-67 assessment (Spearman rank correlation, rsp = 0.91; P = 0.0001; n = 674) but only weak correlation between either semiquantitative or quantitative Ki-67 and S-phase fraction (rsp = 0.12 and rsp = 0.15, respectively). Ki-67 (overall median, 2%) was independent of tumor size and modestly related to other measures of tumor aggressiveness. Using a cutpoint of 5% (percentage of tumor cells), cases with high Ki-67 exhibited a significantly shorter disease-free survival (Padj = 0.004). In multivariate analysis, high Ki-67 was associated with a 1.8-fold increased risk of recurrence (P = 0.001). In the subgroup with S-phase data, the adjusted relative risk (hazard ratio, 1.9; P = 0.02) was unchanged by inclusion of S phase in the model. This suggests that Ki-67 provides significant independent prognostic information in addition to that contained in tumor size and S-phase fraction.

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