Ki-67 As Prognostic Marker in Early Breast Cancer: a Meta-analysis of Published Studies Involving 12,155 Patients

Overview

Journal Br J Cancer

Specialty Oncology

Date 2007 Apr 25

PMID 17453008

Citations 382

Authors

E de Azambuja

F Cardoso

G de Castro Jr

M Colozza

M S Mano

V Durbecq

C Sotiriou

D Larsimont

M J Piccart-Gebhart

M Paesmans

Affiliations

Soon will be listed here.

Abstract

The Ki-67 antigen is used to evaluate the proliferative activity of breast cancer (BC); however, Ki-67's role as a prognostic marker in BC is still undefined. In order to better define the prognostic value of Ki-67/MIB-1, we performed a meta-analysis of studies that evaluated the impact of Ki-67/MIB-1 on disease-free survival (DFS) and/or on overall survival (OS) in early BC. Sixty-eight studies were identified and 46 studies including 12 155 patients were evaluable for our meta-analysis; 38 studies were evaluable for the aggregation of results for DFS, and 35 studies for OS. Patients were considered to present positive tumours for the expression of Ki-67/MIB-1 according to the cut-off points defined by the authors. Ki-67/MIB-1 positivity is associated with higher probability of relapse in all patients (HR=1.93 (95% confidence interval (CI): 1.74-2.14); P<0.001), in node-negative patients (HR=2.31 (95% CI: 1.83-2.92); P<0.001) and in node-positive patients (HR=1.59 (95% CI: 1.35-1.87); P<0.001). Furthermore, Ki-67/MIB-1 positivity is associated with worse survival in all patients (HR=1.95 (95% CI: 1.70-2.24; P<0.001)), node-negative patients (HR=2.54 (95% CI: 1.65-3.91); P<0.001) and node-positive patients (HR=2.33 (95% CI: 1.83-2.95); P<0.001). Our meta-analysis suggests that Ki-67/MIB-1 positivity confers a higher risk of relapse and a worse survival in patients with early BC.

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References

McShane L, Altman D, Sauerbrei W, Taube S, Gion M, Clark G . Reporting recommendations for tumor marker prognostic studies. J Clin Oncol. 2005; 23(36):9067-72. DOI: 10.1200/JCO.2004.01.0454. View

Alonzo T . Standards for reporting prognostic tumor marker studies. J Clin Oncol. 2005; 23(36):9053-4. DOI: 10.1200/JCO.2005.04.3778. View

Kroger N, Milde-Langosch K, Riethdorf S, Schmoor C, Schumacher M, Zander A . Prognostic and predictive effects of immunohistochemical factors in high-risk primary breast cancer patients. Clin Cancer Res. 2006; 12(1):159-68. DOI: 10.1158/1078-0432.CCR-05-1340. View

Costarelli L, Piro F, Fortunato L, Vitelli C, Farina M, Taffuri M . [Predictive variables of lymphatic metastasis in breast carcinoma with a diameter below 2 cm]. Suppl Tumori. 2006; 4(3):S172. View

Pierga J, Leroyer A, Viehl P, Mosseri V, Chevillard S, Magdelenat H . Long term prognostic value of growth fraction determination by Ki-67 immunostaining in primary operable breast cancer. Breast Cancer Res Treat. 1996; 37(1):57-64. DOI: 10.1007/BF01806632. View

Pietilainen T, Lipponen P, Aaltomaa S, Eskelinen M, Kosma V, Syrjanen K . The important prognostic value of Ki-67 expression as determined by image analysis in breast cancer. J Cancer Res Clin Oncol. 1996; 122(11):687-92. DOI: 10.1007/BF01209033. View

Querzoli P, Albonico G, Ferretti S, Rinaldi R, Magri E, Indelli M . MIB-1 proliferative activity in invasive breast cancer measured by image analysis. J Clin Pathol. 1996; 49(11):926-30. PMC: 500834. DOI: 10.1136/jcp.49.11.926. View

Railo M, Lundin J, Haglund C, von Smitten K, von Boguslawsky K, Nordling S . Ki-67, p53, Er-receptors, ploidy and S-phase as prognostic factors in T1 node negative breast cancer. Acta Oncol. 1997; 36(4):369-74. DOI: 10.3109/02841869709001282. View

Thor A, Liu S, Moore 2nd D, Edgerton S . Comparison of mitotic index, in vitro bromodeoxyuridine labeling, and MIB-1 assays to quantitate proliferation in breast cancer. J Clin Oncol. 1999; 17(2):470-7. DOI: 10.1200/JCO.1999.17.2.470. View

10.

Harbeck N, Dettmar P, Thomssen C, Berger U, Ulm K, Kates R . Risk-group discrimination in node-negative breast cancer using invasion and proliferation markers: 6-year median follow-up. Br J Cancer. 1999; 80(3-4):419-26. PMC: 2362313. DOI: 10.1038/sj.bjc.6690373. View

11.

Clahsen P, van de Velde C, Duval C, Pallud C, Mandard A, van den Broek L . The utility of mitotic index, oestrogen receptor and Ki-67 measurements in the creation of novel prognostic indices for node-negative breast cancer. Eur J Surg Oncol. 1999; 25(4):356-63. DOI: 10.1053/ejso.1999.0657. View

12.

Perou C, Jeffrey S, van de Rijn M, Rees C, Eisen M, Ross D . Distinctive gene expression patterns in human mammary epithelial cells and breast cancers. Proc Natl Acad Sci U S A. 1999; 96(16):9212-7. PMC: 17759. DOI: 10.1073/pnas.96.16.9212. View

13.

Rudolph P, MacGrogan G, Bonichon F, Frahm S, de Mascarel I, Trojani M . Prognostic significance of Ki-67 and topoisomerase IIalpha expression in infiltrating ductal carcinoma of the breast. A multivariate analysis of 863 cases. Breast Cancer Res Treat. 1999; 55(1):61-71. DOI: 10.1023/a:1006159016703. View

14.

Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M . A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004; 351(27):2817-26. DOI: 10.1056/NEJMoa041588. View

15.

Wang Y, Klijn J, Zhang Y, Sieuwerts A, Look M, Yang F . Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet. 2005; 365(9460):671-9. DOI: 10.1016/S0140-6736(05)17947-1. View

16.

Erdem O, Dursun A, Coskun U, Gunel N . The prognostic value of p53 and c-erbB-2 expression, proliferative activity and angiogenesis in node-negative breast carcinoma. Tumori. 2005; 91(1):46-52. DOI: 10.1177/030089160509100109. View

17.

Pestalozzi B, Luporsi-Gely E, Jost L, Bergh J . ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and follow-up of primary breast cancer. Ann Oncol. 2005; 16 Suppl 1:i7-9. DOI: 10.1093/annonc/mdi825. View

18.

. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005; 365(9472):1687-717. DOI: 10.1016/S0140-6736(05)66544-0. View

19.

Glinsky G, Berezovska O, Glinskii A . Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. J Clin Invest. 2005; 115(6):1503-21. PMC: 1136989. DOI: 10.1172/JCI23412. View

20.

Tsutsui S, Yasuda K, Suzuki K, Tahara K, Higashi H, Era S . Macrophage infiltration and its prognostic implications in breast cancer: the relationship with VEGF expression and microvessel density. Oncol Rep. 2005; 14(2):425-31. View