Re-evaluating adjuvant breast cancer trials

Assessing hormone receptor status by immunohistochemical versus extraction assays

Meredith M. Regan, Giuseppe Viale, Mauro G. Mastropasqua, Eugenio Maiorano, Rastko Golouh, Antonino Carbone, Bob Brown, Mart Suurküla, Gerald Langman, Luca Mazzucchelli, Stephen Braye, Piergiovanni Grigolato, Richard D. Gelber, Monica Castiglione-Gertsch, Karen N. Price, Alan S. Coates, Aron Goldhirsch, Barry Gusterson

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Abstract

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% (κ = 0.48) for PgR among postmenopausal patients to 88% (κ = 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.

Original languageEnglish
Pages (from-to)1571-1581
Number of pages11
JournalJournal of the National Cancer Institute
Volume98
Issue number21
DOIs
Publication statusPublished - Nov 1 2006

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Hormones
Breast Neoplasms
Progesterone Receptors
Estrogen Receptors
Disease-Free Survival
Therapeutics
Neoplasms
Steroid Receptors
Random Allocation
Proportional Hazards Models
Lymph Nodes
Pathology
Recurrence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Re-evaluating adjuvant breast cancer trials : Assessing hormone receptor status by immunohistochemical versus extraction assays. / Regan, Meredith M.; Viale, Giuseppe; Mastropasqua, Mauro G.; Maiorano, Eugenio; Golouh, Rastko; Carbone, Antonino; Brown, Bob; Suurküla, Mart; Langman, Gerald; Mazzucchelli, Luca; Braye, Stephen; Grigolato, Piergiovanni; Gelber, Richard D.; Castiglione-Gertsch, Monica; Price, Karen N.; Coates, Alan S.; Goldhirsch, Aron; Gusterson, Barry.

In: Journal of the National Cancer Institute, Vol. 98, No. 21, 01.11.2006, p. 1571-1581.

Research output: Contribution to journalArticle

Regan, MM, Viale, G, Mastropasqua, MG, Maiorano, E, Golouh, R, Carbone, A, Brown, B, Suurküla, M, Langman, G, Mazzucchelli, L, Braye, S, Grigolato, P, Gelber, RD, Castiglione-Gertsch, M, Price, KN, Coates, AS, Goldhirsch, A & Gusterson, B 2006, 'Re-evaluating adjuvant breast cancer trials: Assessing hormone receptor status by immunohistochemical versus extraction assays', Journal of the National Cancer Institute, vol. 98, no. 21, pp. 1571-1581. https://doi.org/10.1093/jnci/djj415
Regan, Meredith M. ; Viale, Giuseppe ; Mastropasqua, Mauro G. ; Maiorano, Eugenio ; Golouh, Rastko ; Carbone, Antonino ; Brown, Bob ; Suurküla, Mart ; Langman, Gerald ; Mazzucchelli, Luca ; Braye, Stephen ; Grigolato, Piergiovanni ; Gelber, Richard D. ; Castiglione-Gertsch, Monica ; Price, Karen N. ; Coates, Alan S. ; Goldhirsch, Aron ; Gusterson, Barry. / Re-evaluating adjuvant breast cancer trials : Assessing hormone receptor status by immunohistochemical versus extraction assays. In: Journal of the National Cancer Institute. 2006 ; Vol. 98, No. 21. pp. 1571-1581.
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abstract = "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{\%} (κ = 0.48) for PgR among postmenopausal patients to 88{\%} (κ = 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.",
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T1 - Re-evaluating adjuvant breast cancer trials

T2 - Assessing hormone receptor status by immunohistochemical versus extraction assays

AU - Regan, Meredith M.

AU - Viale, Giuseppe

AU - Mastropasqua, Mauro G.

AU - Maiorano, Eugenio

AU - Golouh, Rastko

AU - Carbone, Antonino

AU - Brown, Bob

AU - Suurküla, Mart

AU - Langman, Gerald

AU - Mazzucchelli, Luca

AU - Braye, Stephen

AU - Grigolato, Piergiovanni

AU - Gelber, Richard D.

AU - Castiglione-Gertsch, Monica

AU - Price, Karen N.

AU - Coates, Alan S.

AU - Goldhirsch, Aron

AU - Gusterson, Barry

PY - 2006/11/1

Y1 - 2006/11/1

N2 - 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% (κ = 0.48) for PgR among postmenopausal patients to 88% (κ = 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.

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