American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer

Overview

Journal Arch Pathol Lab Med

Specialty Pathology

Date 2010 Jun 8

PMID 20524868

Citations 237

Authors

M Elizabeth H Hammond

Daniel F Hayes

Mitch Dowsett

D Craig Allred

Karen L Hagerty

Sunil Badve

Patrick L Fitzgibbons

Glenn Francis

Neil S Goldstein

Malcolm Hayes

David G Hicks

Susan Lester

Richard Love

Pamela B Mangu

Lisa McShane

Keith Miller

C Kent Osborne

Soonmyung Paik

Jane Perlmutter

Anthony Rhodes

Hironobu Sasano

Jared N Schwartz

Fred C G Sweep

Sheila Taube

Emina Emilia Torlakovic

Paul Valenstein

Giuseppe Viale

Daniel Visscher

Thomas Wheeler

R Bruce Williams

James L Wittliff

Antonio C Wolff

Affiliations

Soon will be listed here.

Abstract

Purpose: To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers.

Methods: The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance.

Results: Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate (false negative or false positive). Most of the issues with testing have occurred because of variation in preanalytic variables, thresholds for positivity, and interpretation criteria.

Recommendations: The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, reproducible assay performance is proposed. Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials.

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References

Harvey J, Clark G, Osborne C, Allred D . Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol. 1999; 17(5):1474-81. DOI: 10.1200/JCO.1999.17.5.1474. View

Gutman S . Regulatory issues in tumor marker development. Semin Oncol. 2002; 29(3):294-300. DOI: 10.1053/sonc.2002.33140. View

Mohsin S, Weiss H, Havighurst T, Clark G, Berardo M, Roanh L . Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study. Mod Pathol. 2004; 17(12):1545-54. DOI: 10.1038/modpathol.3800229. View

Badve S, Baehner F, Gray R, Childs B, Maddala T, Liu M . Estrogen- and progesterone-receptor status in ECOG 2197: comparison of immunohistochemistry by local and central laboratories and quantitative reverse transcription polymerase chain reaction by central laboratory. J Clin Oncol. 2008; 26(15):2473-81. DOI: 10.1200/JCO.2007.13.6424. View

Regan M, Viale G, Mastropasqua M, Maiorano E, Golouh R, Carbone A . Re-evaluating adjuvant breast cancer trials: assessing hormone receptor status by immunohistochemical versus extraction assays. J Natl Cancer Inst. 2006; 98(21):1571-81. DOI: 10.1093/jnci/djj415. View

Ogawa Y, Moriya T, Kato Y, Oguma M, Ikeda K, Takashima T . Immunohistochemical assessment for estrogen receptor and progesterone receptor status in breast cancer: analysis for a cut-off point as the predictor for endocrine therapy. Breast Cancer. 2004; 11(3):267-75. DOI: 10.1007/BF02984548. View

Lockwood C, Ricciardelli C, Raymond W, Seshadri R, McCaul K, Horsfall D . A simple index using video image analysis to predict disease outcome in primary breast cancer. Int J Cancer. 1999; 84(3):203-8. DOI: 10.1002/(sici)1097-0215(19990621)84:3<203::aid-ijc1>3.0.co;2-u. View

Viale G, Regan M, Maiorano E, Mastropasqua M, Golouh R, Perin T . 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. 2008; 26(9):1404-10. DOI: 10.1200/JCO.2007.10.6393. View

Fitzgibbons P, Murphy D, Hammond M, Allred D, Valenstein P . Recommendations for validating estrogen and progesterone receptor immunohistochemistry assays. Arch Pathol Lab Med. 2010; 134(6):930-5. DOI: 10.5858/134.6.930. View

10.

Knight 3rd W, Osborne C, McGuire W . Hormone receptors in primary and advanced breast cancer. Clin Endocrinol Metab. 1980; 9(2):361-8. DOI: 10.1016/s0300-595x(80)80038-7. View

11.

Phillips T, Murray G, Wakamiya K, Askaa J, Huang D, Welcher R . Development of standard estrogen and progesterone receptor immunohistochemical assays for selection of patients for antihormonal therapy. Appl Immunohistochem Mol Morphol. 2007; 15(3):325-31. DOI: 10.1097/01.pai.0000213135.16783.bc. View

12.

Barnes D, Harris W, Smith P, Millis R, Rubens R . Immunohistochemical determination of oestrogen receptor: comparison of different methods of assessment of staining and correlation with clinical outcome of breast cancer patients. Br J Cancer. 1996; 74(9):1445-51. PMC: 2074773. DOI: 10.1038/bjc.1996.563. View

13.

Elledge R, Green S, Pugh R, Allred D, Clark G, Hill J . Estrogen receptor (ER) and progesterone receptor (PgR), by ligand-binding assay compared with ER, PgR and pS2, by immuno-histochemistry in predicting response to tamoxifen in metastatic breast cancer: a Southwest Oncology Group Study. Int J Cancer. 2001; 89(2):111-7. 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.

Goldstein N, Ferkowicz M, Odish E, Mani A, Hastah F . Minimum formalin fixation time for consistent estrogen receptor immunohistochemical staining of invasive breast carcinoma. Am J Clin Pathol. 2003; 120(1):86-92. DOI: 10.1309/QPHD-RB00-QXGM-UQ9N. View

16.

Osborne C, Yochmowitz M, Knight 3rd W, McGuire W . The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer. 1980; 46(12 Suppl):2884-8. DOI: 10.1002/1097-0142(19801215)46:12+<2884::aid-cncr2820461429>3.0.co;2-u. View

17.

Stendahl M, Ryden L, Nordenskjold B, Jonsson P, Landberg G, Jirstrom K . High progesterone receptor expression correlates to the effect of adjuvant tamoxifen in premenopausal breast cancer patients. Clin Cancer Res. 2006; 12(15):4614-8. DOI: 10.1158/1078-0432.CCR-06-0248. View

18.

Gown A . Unmasking the mysteries of antigen or epitope retrieval and formalin fixation. Am J Clin Pathol. 2004; 121(2):172-4. DOI: 10.1309/9G5F-Y3U3-QB4R-15DR. View

19.

Taylor C, Levenson R . Quantification of immunohistochemistry--issues concerning methods, utility and semiquantitative assessment II. Histopathology. 2006; 49(4):411-24. DOI: 10.1111/j.1365-2559.2006.02513.x. View

20.

Yaziji H, Taylor C, Goldstein N, Dabbs D, Hammond E, Hewlett B . Consensus recommendations on estrogen receptor testing in breast cancer by immunohistochemistry. Appl Immunohistochem Mol Morphol. 2008; 16(6):513-20. DOI: 10.1097/PAI.0b013e31818a9d3a. View