Ki-67 Expression Gives Additional Prognostic Information on St. Gallen 2007 and Adjuvant! Online Risk Categories in Early Breast Cancer

Abstract

Background. We sought to determine the significance of Ki-67, one of the tumor cell proliferation markers, as a useful prognostic factor in early breast cancer. Results. Univariate analysis determined that tumor size, lymph node involvement, histologic grade, estrogen receptor, progesterone receptor, bcl-2, and Ki-67 (C10%) were statistically significant for both overall survival (OS) and distant metastasis-free survival (DFS). Of these factors, lymph node involvement and high Ki-67 expression were identified as independent prognostic factors for OS and DFS on the basis of multivariate analysis. The survivals of intermediate-and high-risk groups according to 2007 St. Gallen consensus were further separated by Ki-67 expression level (5-year DFS rate = 91.9% vs. 86.3% for Ki-67 \ 10% and C10%, respectively in intermediate-risk group (P = .01); 5-year DFS rate = 82.5% vs. 61.4% for Ki-67 \ 10% and C10%, respectively in high-risk group (P = .01)). The survivals of low-and high-risk groups according to Adjuvant! Online were further separated by Ki-67 expression level (5-year DFS rate = 97.8% vs. 89.5% for Ki-67 \ 10% and C10%, respectively in low-risk group (P = .02); 5-year DFS rate = 9.4% vs. 82.6% for Ki-67 \ 10% and C10% in highrisk group (P = .005)). Conclusions. Ki-67 is an independent prognostic factor for DFS and OS in early breast cancer and can provide additional prognostic information on the risk stratification with the use of the 2007 St. Gallen consensus and Adjuvant! Online.

The prognostic value of Ki67 is dependent on estrogen receptor status and histological grade in premenopausal patients with node-negative breast cancer

“…This study confirms that Ki67 is a prognostic marker for distant recurrence [5][6][7]18,19,21,22 and overall survival [5][6][7]17,18,[20][21][22] in lymph node-negative breast cancer. Interestingly, it only adds prognostic information in the ER-positive group and in patients with histological grade 2, the latter which to our knowledge no earlier study on Ki67 has addressed.…”

“…25 Even though our patient material is not equivalent to the patient material in the above-mentioned studies, it nevertheless suggests that a division of ER-positive disease can be achieved by merely analyzing one marker of proliferation, in line with another recent publication on Ki67. 22 Histological grade was not an independent prognostic factor in this study, not even in the subgroup of medically untreated patients, in which Ki67 was of independent prognostic value. Because of studies showing interobserver variability, 13,26,27 the value of histological grade has been questioned.…”

“…26,27 As far as Ki67 is concerned, we found a good correlation between three readers as well as between manual counting and semi-quantitative analysis, in line with earlier publications. 19 Evaluation of Ki67 can be done both on whole section 17,[19][20][21][22]30 and tissue microarray. 18 We chose tissue microarray as it is less time consuming, allows assessments of large numbers of tumors on a single slide, and as earlier studies have shown a good agreement of Ki67 quantification between tissue microarray and large section.…”

“…13 The predefined cutoff we chose, 20%, set at the seventh decile, is within the range of cutoffs from earlier published studies (5-30%), defined as optimized cut-points, median cut-points, or categorization in three groups. 3,[17][18][19][20]22,30 Optimal cutoffs of 25% for high-grade tumors sensitive to chemotherapy, and 10% for slowly proliferating tumors have been suggested. 30 In line with the results in an earlier publication, a cutoff at the seventh decile defines a high-risk population, likely to benefit from adjuvant chemotherapy.…”

“…5,8,[17][18][19][20][21][22] It is also a predictor of better response to chemotherapy. 5,7 Furthermore, as Ki67 is also affordable and easily assessed on paraffin-embedded tumor material, it has been widely used, even though it has not been generally recommended for use by all guidelines, 1,2 as there is no international standardization for the method.…”