Top

Published in:

Open Access 01-05-2009 | Breast Oncology

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

Authors: So-Youn Jung, MD, Wonshik Han, MD, PhD, Jong Won Lee, MD, Eunyoung Ko, MD, Eunkyu Kim, MD, Jong-Han Yu, MD, Hyeong-Gon Moon, MD, In Ae Park, MD, PhD, Do-Youn Oh, MD, PhD, Seock-Ah Im, MD, PhD, Tae-You Kim, MD, PhD, Ki-Tae Hwang, MD, PhD, Sung-Won Kim, MD, PhD, Dong-Young Noh, MD, PhD

Published in: Annals of Surgical Oncology | Issue 5/2009

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.

Methods

A total of 1080 consecutive patients with stage I or II breast cancer that underwent surgery between 1998 and 2003 were enrolled. Patients were categorized on the basis of the 2007 St. Gallen consensus and Adjuvant! Online. The expression of Ki-67 in the tumor was assayed by immunohistochemistry (cutoff value, 10%).

Results

Univariate analysis determined that tumor size, lymph node involvement, histologic grade, estrogen receptor, progesterone receptor, bcl-2, and Ki-67 (≥10%) 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 ≥10%, respectively in intermediate-risk group (P = .01); 5-year DFS rate = 82.5% vs. 61.4% for Ki-67 < 10% and ≥10%, 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 ≥10%, respectively in low-risk group (P = .02); 5-year DFS rate = 9.4% vs. 82.6% for Ki-67 < 10% and ≥10% in high-risk 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.

Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687–717.

Goldhirsch A, Wood WC, Gelber RD, et al. Meeting highlights: updated international expert consensus on the primary therapy of early breast cancer. J Clin Oncol. 2003;21:3357–65.PubMedCrossRef

Boyages J, Chua B, Taylor R, et al. Use of the St Gallen classification for patients with node-negative breast cancer may lead to overuse of adjuvant chemotherapy. Br J Surg. 2002;89:789–96.PubMedCrossRef

Iwamoto E, Fukutomi T, Akashi-Tanaka S. Validation and problems of St Gallen recommendations of adjuvant therapy for node-negative invasive breast cancer in Japanese patients. Jpn J Clin Oncol. 2001;31:259–62.PubMedCrossRef

Ravdin PM, Siminoff LA, Davis GJ, et al. Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol. 2001;19:980–91.PubMed

Buyse M, Loi S, van’t Veer L, et al. Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst. 2006;98:1183–92.PubMedCrossRef

Galea MH, Blamey RW, Elston CE, Ellis IO. The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat. 1992;22:207–19.PubMedCrossRef

Ahn SH, Son BH, Kim SW, et al. Poor outcome of hormone receptor-positive breast cancer at very young age is due to tamoxifen resistance: nationwide survival data in Korea—a report from the Korean Breast Cancer Society. J Clin Oncol. 2007;25:2360–8.PubMedCrossRef

Sun JM, Han W, Im SA, et al. A combination of HER-2 status and the St. Gallen classification provides useful information on prognosis in lymph node-negative breast carcinoma. Cancer. 2004;101:2516–22.PubMedCrossRef

10.

Harris L, Fritsche H, Mennel R, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25:5287–312.PubMedCrossRef

11.

Colozza M, Azambuja E, Cardoso F, et al. Proliferative markers as prognostic and predictive tools in early breast cancer: where are we now? Ann Oncol. 2005;16:1723–39.PubMedCrossRef

12.

Gerdes J, Li L, Schlueter C, et al. Immunobiochemical and molecular biologic characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67. Am J Pathol. 1991;138:867–73.PubMed

13.

Cher ML, Chew K, Rosenau W, Carroll PR. Cellular proliferation in prostatic adenocarcinoma as assessed by bromodeoxyuridine uptake and Ki-67 and PCNA expression. Prostate. 1995;26:87–93.PubMedCrossRef

14.

Dowsett M, Smith IE, Ebbs SR, et al. Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer. J Natl Cancer Inst. 2007;99:167–70.PubMedCrossRef

15.

Caly M, Genin P, Ghuzlan AA, et al. Analysis of correlation between mitotic index, MIB1 score and S-phase fraction as proliferation markers in invasive breast carcinoma Methodological aspects and prognostic value in a series of 257 cases. Anticancer Res. 2004;24:3283–8.PubMed

16.

Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–26.PubMedCrossRef

17.

de Azambuja E, Cardoso F, de Castro G Jr, et al. Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer. 2007;96:1504–13.PubMedCrossRef

18.

Trihia H, Murray S, Price K, et al. Ki-67 expression in breast carcinoma: its association with grading systems, clinical parameters, and other prognostic factors—a surrogate marker?. Cancer. 2003;97:1321–31.PubMedCrossRef

19.

Molino A, Micciolo R, Turazza M, et al. Ki-67 immunostaining in 322 primary breast cancers: associations with clinical and pathological variables and prognosis. Int J Cancer. 1997;74:433–7.PubMedCrossRef

20.

Goldhirsch A, Wood WC, Gelber RD, et al. Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007. Ann Oncol. 2007;18:1133–44.PubMedCrossRef

21.

Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19:403–10.PubMedCrossRef

22.

Billgren AM, Tani E, Liedberg A, et al. Prognostic significance of tumor cell proliferation analyzed in fine needle aspirates from primary breast cancer. Breast Cancer Res Treat. 2002;71:161–70.PubMedCrossRef

23.

Brown RW, Allred CD, Clark GM, et al. Prognostic value of Ki-67 compared to S-phase fraction in axillary node-negative breast cancer. Clin Cancer Res. 1996;2:585–92.PubMed

24.

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;91:46–52.PubMed

25.

Rudolph P, Alm P, Heidebrecht HJ, et al. Immunologic proliferation marker Ki-S2 as prognostic indicator for lymph node-negative breast cancer. J Natl Cancer Inst. 1999;91:271–8.PubMedCrossRef

26.

Pietilainen T, Lipponen P, Aaltomaa S, et al. The important prognostic value of Ki-67 expression as determined by image analysis in breast cancer. J Cancer Res Clin Oncol. 1996;122:687–92.PubMedCrossRef

27.

Jacquemier J, Ginestier C, Rougemont J, et al. Protein expression profiling identifies subclasses of breast cancer and predicts prognosis. Cancer Res. 2005;65:767–79.PubMed

28.

Wang Y, Klijn JG, Zhang Y, et al. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet. 2005;365:671–9.PubMed

29.

van de Vijver MJ, He YD, van’t Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009.PubMedCrossRef

30.

Malaise EP, Chavaudra N, Tubiana M. The relationship between growth rate, labelling index and histological type of human solid tumours. Eur J Cancer. 1973;9:305–12.PubMed

31.

Dean PN, Dolbeare F, Gratzner H, et al. Cell-cycle analysis using a monoclonal antibody to BrdUrd. Cell Tissue Kinet. 1984;17:427–36.PubMed

32.

Quirke P, Dyson JE. Flow cytometry: methodology and applications in pathology. J Pathol. 1986;149:79–87.PubMedCrossRef

33.

Thor AD, Liu S, Moore DH II, Edgerton SM. Comparison of mitotic index, in vitro bromodeoxyuridine labeling, and MIB-1 assays to quantitate proliferation in breast cancer. J Clin Oncol. 1999;17:470–7.PubMed

34.

Lau R, Grimson R, Sansome C, et al. Low levels of cell cycle inhibitor p27kip1 combined with high levels of Ki-67 predict shortened disease-free survival in T1 and T2 invasive breast carcinomas. Int J Oncol. 2001;18:17–23.PubMed

35.

Railo M, Lundin J, Haglund C, et al. Ki-67, p53, ER receptors, ploidy and S phase as long-term prognostic factors in T1 node-negative breast cancer. Tumour Biol. 2007;28:45–51.PubMedCrossRef

36.

Spyratos F, Ferrero-Pous M, Trassard M, et al. Correlation between MIB-1 and other proliferation markers: clinical implications of the MIB-1 cutoff value. Cancer. 2002;94:2151–9.PubMedCrossRef

37.

Volpi A, Nanni O, De Paola F, et al. HER-2 expression and cell proliferation: prognostic markers in patients with node-negative breast cancer. J Clin Oncol. 2003;21:2708–12.PubMedCrossRef

38.

Veronese SM, Gambacorta M, Gottardi O, et al. Proliferation index as a prognostic marker in breast cancer. Cancer. 1993;71:3926–31.PubMedCrossRef

39.

Palazzi M, De Tomasi D, D’Affronto C, et al. Are international guidelines for the prescription of adjuvant treatment for early breast cancer followed in clinical practice? Results of a population-based study on 1547 patients. Tumori. 2002;88:503–6.PubMed

40.

Roila F, Ballatori E, Patoia L, et al. Adjuvant systemic therapies in women with breast cancer: an audit of clinical practice in Italy. Ann Oncol. 2003;14:843–8.PubMedCrossRef

41.

Olivotto IA, Bajdik CD, Ravdin PM, et al. Population-based validation of the prognostic model Adjuvant! for early breast cancer. J Clin Oncol. 2005;23:2716–25.PubMedCrossRef

Title: Ki-67 Expression Gives Additional Prognostic Information on St. Gallen 2007 and Adjuvant! Online Risk Categories in Early Breast Cancer
Authors: So-Youn Jung, MD
Wonshik Han, MD, PhD
Jong Won Lee, MD
Eunyoung Ko, MD
Eunkyu Kim, MD
Jong-Han Yu, MD
Hyeong-Gon Moon, MD
In Ae Park, MD, PhD
Do-Youn Oh, MD, PhD
Seock-Ah Im, MD, PhD
Tae-You Kim, MD, PhD
Ki-Tae Hwang, MD, PhD
Sung-Won Kim, MD, PhD
Dong-Young Noh, MD, PhD
Publication date: 01-05-2009
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 5/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-009-0334-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 5/2009

Predictive Factors of Level IIb Lymph Node Metastasis in Patients with Papillary Thyroid Carcinoma

Decrease in Hemoglobin Levels Following Surgery Influences the Outcome in Head and Neck Cancer Patients Treated with Accelerated Postoperative Radiotherapy

The Importance of Measuring the Measures

Clinical Significance of Splenic Hilar Lymph Node Metastasis in Proximal Gastric Cancer

Preoperative Needle Biopsy as a Potential Quality Measure in Breast Cancer Surgery

Liver Resection with Portal Vein Thrombectomy for Hepatocellular Carcinoma With Vascular Invasion