© The Author 2006. Published by Oxford University Press.
ARTICLE |
Re-evaluating Adjuvant Breast Cancer Trials: Assessing Hormone Receptor Status by Immunohistochemical Versus Extraction Assays
For the International Breast Cancer Study Group (IBCSG)
Affiliations of authors: IBCSG Statistical Center, Dana-Farber Cancer Institute, Boston, MA (MMR, RDG, KNP); Harvard School of Public Health, Boston, MA (MMR, RDG); Department of Pathology, European Institute of Oncology, University of Milan, Milan, Italy (GV, MGM); Department of Pathology, University of Bari, Bari, Italy (EM); The Institute of Oncology, Ljubljana, Slovenia (RG); Division of Pathology, Centro di Riferimento Oncologico, Aviano, Italy (AC); Department of Pathology, Istituto Nazionale Tumori, Milan, Italy (AC); Melbourne Pathology, Collingwood, Victoria, Australia (BB); Department of Pathology, Göteborg/Sahlgrenska University Hospital, Göteborg, Sweden (MS); Department of Anatomical Pathology, University of Cape Town, and Groote Schuur Hospital, Cape Town, South Africa (GL); Bern Institut für Pathologie der Universität Bern, Swiss Group for Clinical Cancer Research, Bern, Switzerland (LM); Australian New Zealand Breast Cancer Trials Group, University of Newcastle, Newcastle, and Anatomical Pathology, Hunter Area Pathology Service, John Hunter Hospital, New Lambton Heights, New South Wales, Australia (SB); Oncologia Medica-Spedali Civili, Brescia, Italy (PG); Frontier Science and Technology Research Foundation, Boston, MA (RDG, KNP); IBCSG Coordinating Center, Bern, Switzerland (MCG); The Cancer Council Australia, Australian New Zealand Breast Cancer Trials Group and School of Public Health, University of Sydney, Sydney, Australia (ASC); Oncology Institute of Southern Switzerland, Bellinzona, Lugano, Mendrisio, Switzerland (AG); European Institute of Oncology, Milan, Italy (AG); Division of Cancer Sciences and Molecular Pathology, Western Infirmary, University of Glasgow, UK (BG).
Correspondence to: Meredith M. Regan, ScD, IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115 (e-mail: mregan{at}jimmy.harvard.edu).
Background: Tumor levels of steroid hormone receptors, a factor used to select adjuvant treatment for early-stage breast cancer, are currently determined with immunohistochemical assays. These assays have a discordance of 10%–30% with previously used extraction assays. We assessed the concordance and predictive value of hormone receptor status as determined by immunohistochemical and extraction assays on specimens from International Breast Cancer Study Group Trials VIII and IX. These trials predominantly used extraction assays and compared adjuvant chemoendocrine therapy with endocrine therapy alone among pre- and postmenopausal patients with lymph node–negative breast cancer. Trial conclusions were that combination therapy provided a benefit to pre- and postmenopausal patients with estrogen receptor (ER)–negative tumors but not to ER-positive postmenopausal patients. ER-positive premenopausal patients required further study. Methods: Tumor specimens from 571 premenopausal and 976 postmenopausal patients on which extraction assays had determined ER and progesterone receptor (PgR) levels before randomization from October 1, 1988, through October 1, 1999, were re-evaluated with an immunohistochemical assay in a central pathology laboratory. The endpoint was disease-free survival. Hazard ratios of recurrence or death for treatment comparisons were estimated with Cox proportional hazards regression models, and discriminatory ability was evaluated with the c index. All statistical tests were two-sided. Results: Concordance of hormone receptor status determined by both assays ranged from 74% (
= 0.48) for PgR among postmenopausal patients to 88% ( = 0.66) for ER in postmenopausal patients. Hazard ratio estimates were similar for the association between disease-free survival and ER status (among all patients) or PgR status (among postmenopausal patients) as determined by the two methods. However, among premenopausal patients treated with endocrine therapy alone, the discriminatory ability of PgR status as determined by immunohistochemical assay was statistically significantly better (c index = 0.60 versus 0.51; P = .003) than that determined by extraction assay, and so immunohistochemically determined PgR status could predict disease-free survival. Conclusions: Trial conclusions in which ER status (for all patients) or PgR status (for postmenopausal patients) was determined by immunohistochemical assay supported those determined by extraction assays. However, among premenopausal patients, trial conclusions drawn from PgR status differed—immunohistochemically determined PgR status could predict response to endocrine therapy, unlike that determined by the extraction assay.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. E. Brock, J. L. Hornick, A. L. Richardson, D. A. Dillon, and S. C. Lester A Comparison of Estrogen Receptor SP1 and 1D5 Monoclonal Antibodies in Routine Clinical Use Reveals Similar Staining Results Am J Clin Pathol, September 1, 2009; 132(3): 396 - 401. [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. P.S. Dunphy and J. S. Lewis Radiopharmaceuticals in Preclinical and Clinical Development for Monitoring of Therapy with PET J. Nucl. Med., May 1, 2009; 50(Suppl_1): 106S - 121S. [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]
|
|
|
|
 |
|
 R A Walker Immunohistochemical markers as predictive tools for breast cancer J. Clin. Pathol., June 1, 2008; 61(6): 689 - 696. [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]
|
|
|
|
|
|
G. Viale, M. M. Regan, E. Maiorano, M. G. Mastropasqua, R. Golouh, T. Perin, R. W. Brown, A. Kovacs, K. Pillay, C. Ohlschlegel, et al. Chemoendocrine Compared With Endocrine Adjuvant Therapies for Node-Negative Breast Cancer: Predictive Value of Centrally Reviewed Expression of Estrogen and Progesterone Receptors--International Breast Cancer Study Group J. Clin. Oncol., March 20, 2008; 26(9): 1404 - 1410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Viale, M. M. Regan, M. G. Mastropasqua, F. Maffini, E. Maiorano, M. Colleoni, K. N. Price, R. Golouh, T. Perin, R. W. Brown, et al. Predictive Value of Tumor Ki-67 Expression in Two Randomized Trials of Adjuvant Chemoendocrine Therapy for Node-Negative Breast Cancer J Natl Cancer Inst, February 6, 2008; 100(3): 207 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Rakha and I. O. Ellis In Reply J. Clin. Oncol., January 10, 2008; 26(2): 336 - 338. [Full Text] [PDF]
|
|
|
|
|
|
G. Viale, M. M. Regan, E. Maiorano, M. G. Mastropasqua, P. Dell'Orto, B. B. Rasmussen, J. Raffoul, P. Neven, Z. Orosz, S. Braye, et al. Prognostic and Predictive Value of Centrally Reviewed Expression of Estrogen and Progesterone Receptors in a Randomized Trial Comparing Letrozole and Tamoxifen Adjuvant Therapy for Postmenopausal Early Breast Cancer: BIG 1-98 J. Clin. Oncol., September 1, 2007; 25(25): 3846 - 3852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Veronesi, P. Maisonneuve, N. Rotmensz, B. Bonanni, P. Boyle, G. Viale, A. Costa, V. Sacchini, R. Travaglini, G. D'Aiuto, et al. Tamoxifen for the Prevention of Breast Cancer: Late Results of the Italian Randomized Tamoxifen Prevention Trial Among Women With Hysterectomy J Natl Cancer Inst, May 2, 2007; 99(9): 727 - 737. [Abstract] [Full Text] [PDF]
|
|