Journal of the National Cancer Institute Advance Access published online on January 29, 2008
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djm289
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© The Author 2008. Published by Oxford University Press.
Predictive Value of Tumor Ki-67 Expression in Two Randomized Trials of Adjuvant Chemoendocrine Therapy for Node-Negative Breast Cancer
On the behalf of the International Breast Cancer Study Group
Affiliations of the authors: Divisions of Pathology and Laboratory Medicine (GV, MGM, FM) and Medical Oncology (MC, AG), European Institute of Oncology, University of Milan, Milan, Italy; International Breast Cancer Study Group (IBCSG) Statistical Center, Dana-Farber Cancer Institute, Frontier Science and Technology Research Foundation, Harvard School of Public Health, Boston, MA (MMR, KNP, RDG); Department of Pathological Anatomy, University of Bari, Bari, Italy (EM); The Institute of Oncology, Ljubljana, Slovenia (RG); Division of Pathology, Centro di Riferimento Oncologico, Aviano, Italy (TP); Melbourne Pathology, Collingwood, Victoria, Australia (RWB); Department of Pathology, Göteborg/Sahlgrenska University Hospital, Göteborg, Sweden (AK); Division of Anatomical Pathology, Department of Clinical Laboratory Sciences, University of Cape Town, National Health Laboratory Services and Groote Schuur Hospital, Cape Town, South Africa (KP); Kantonspital, St Gallen, Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland (CO); Division of Cancer Sciences and Molecular Pathology, Western Infirmary, University of Glasgow, UK (BAG); IBCSG Coordinating Center, Bern, Switzerland (MCG); Oncology Institute of Southern Switzerland, Bellinzona, Switzerland (AG); IBCSG, Bern, Switzerland (ASC); University of Sydney, Australia (ASC)
Correspondence to: Giuseppe Viale, MD, FRCPath, Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Via Ripamoniti 435, Milan, Italy (e-mail: giuseppe.viale{at}ieo.it).
Several small studies have reported that having a high percentage of breast tumor cells that express the proliferation antigen Ki-67 (ie, a high Ki-67 labeling index) predicts better response to neoadjuvant chemotherapy. However, the predictive value of a high Ki-67 labeling index for response to adjuvant chemotherapy is unclear. To investigate whether Ki-67 labeling index predicts response to adjuvant chemoendocrine therapy, we assessed Ki-67 expression in tumor tissue from 1924 (70%) of 2732 patients who were enrolled in two randomized International Breast Cancer Study Group trials of adjuvant chemoendocrine therapy vs endocrine therapy alone for node-negative breast cancer. A high Ki-67 labeling index was associated with other factors that predict poor prognosis. Among the 1521 patients with endocrine-responsive tumors, a high Ki-67 labeling index was associated with worse disease-free survival but the Ki-67 labeling index did not predict the relative efficacy of chemoendocrine therapy compared with endocrine therapy alone. Thus, Ki-67 labeling index was an independent prognostic factor but was not predictive of better response to adjuvant chemotherapy in these studies.
| CONTEXT AND CAVEATS Prior knowledge Some studies have suggested that having a high percentage of breast tumor cells that label with an antibody against the proliferation antigen Ki-67 predicts a better response to primary (ie, neoadjuvant) chemotherapy. Study design A retrospective assessment of the predictive value of a high Ki-67 labeling index for response to therapy among women enrolled in two randomized trials of adjuvant chemoendocrine therapy vs endocrine therapy alone for node-negative breast cancer. Contribution A high Ki-67 labeling index did not predict which women would benefit from further treatment with chemotherapy added to endocrine therapy. Limitations Only women with node-negative breast cancer were included in this study. Implications Other biomarkers are needed to define which women with endocrine-responsive node-negative early breast cancer could benefit from the addition of adjuvant chemotherapy to endocrine therapy.
|
Manuscript received July 5, 2007; revised November 21, 2007; accepted November 27, 2007.
Editorial about this Article
Related Article in JNCI
CiteULike 
Connotea 
Del.icio.us What's this?
J Natl Cancer Inst 2008 100: 159-161.
J Natl Cancer Inst 2008 100: 157.
This article has been cited by other articles:
|
|
 |
|
  S. J. Howell, A. M. Wardley, and A. C. Armstrong Re: Ki67 Index, HER2 Status, and Prognosis of Patients With Luminal B Breast Cancer J Natl Cancer Inst, November 5, 2009; (2009) djp390v1. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Pusztai, J.-H. Jeong, Y. Gong, J. S. Ross, C. Kim, S. Paik, R. Rouzier, F. Andre, G. N. Hortobagyi, N. Wolmark, et al. Evaluation of Microtubule-Associated Protein-Tau Expression As a Prognostic and Predictive Marker in the NSABP-B 28 Randomized Clinical Trial J. Clin. Oncol., September 10, 2009; 27(26): 4287 - 4292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Guarneri, F. Piacentini, G. Ficarra, A. Frassoldati, R. D'Amico, S. Giovannelli, A. Maiorana, G. Jovic, and P. Conte A prognostic model based on nodal status and Ki-67 predicts the risk of recurrence and death in breast cancer patients with residual disease after preoperative chemotherapy Ann. Onc., July 1, 2009; 20(7): 1193 - 1198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Penault-Llorca, F. Andre, C. Sagan, M. Lacroix-Triki, Y. Denoux, V. Verriele, J. Jacquemier, M. C. Baranzelli, F. Bibeau, M. Antoine, et al. Ki67 Expression and Docetaxel Efficacy in Patients With Estrogen Receptor-Positive Breast Cancer J. Clin. Oncol., June 10, 2009; 27(17): 2809 - 2815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. U. Cheang, S. K. Chia, D. Voduc, D. Gao, S. Leung, J. Snider, M. Watson, S. Davies, P. S. Bernard, J. S. Parker, et al. Ki67 Index, HER2 Status, and Prognosis of Patients With Luminal B Breast Cancer J Natl Cancer Inst, May 20, 2009; 101(10): 736 - 750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Margulis, Y. Lotan, P. I. Karakiewicz, Y. Fradet, R. Ashfaq, U. Capitanio, F. Montorsi, P. J. Bastian, M. E. Nielsen, S. C. Muller, et al. Multi-Institutional Validation of the Predictive Value of Ki-67 Labeling Index in Patients With Urinary Bladder Cancer J Natl Cancer Inst, January 21, 2009; 101(2): 114 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Viale, A. Giobbie-Hurder, M. M. Regan, A. S. Coates, M. G. Mastropasqua, P. Dell'Orto, E. Maiorano, G. MacGrogan, S. G. Braye, C. Ohlschlegel, et al. Prognostic and Predictive Value of Centrally Reviewed Ki-67 Labeling Index in Postmenopausal Women With Endocrine-Responsive Breast Cancer: Results From Breast International Group Trial 1-98 Comparing Adjuvant Tamoxifen With Letrozole J. Clin. Oncol., December 1, 2008; 26(34): 5569 - 5575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ravaioli, F. Monti, M. M. Regan, F. Maffini, M. G. Mastropasqua, V. Spataro, M. Castiglione-Gertsch, I. Panzini, L. Gianni, A. Goldhirsch, et al. p27 and Skp2 immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer Ann. Onc., April 1, 2008; 19(4): 660 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Ellis Improving Outcomes for Patients With Hormone Receptor-Positive Breast Cancer: Back to the Drawing Board J Natl Cancer Inst, February 6, 2008; 100(3): 159 - 161. [Full Text] [PDF]
|
|