NCCN Task Force Report: Estrogen Receptor and Progesterone Receptor Testing in Breast Cancer by Immunohistochemistry

The NCCN Task Force on Estrogen Receptor and Progesterone Receptor Testing in Breast Cancer by Immunohistochemistry was convened to critically evaluate the extent to which the presence of the estrogen receptor (ER) and progesterone receptor (PgR) biomarkers in breast cancer serve as prognostic and predictive factors in the adjuvant and metastatic settings, and the ability of immunohistochemical (IHC) detection of ER and PgR to provide an accurate assessment of the expression of these biomarkers in breast cancer tumor tissue. The task force is a multidisciplinary panel of 13 experts in breast cancer who are affiliated with NCCN member institutions and represent the disciplines of pathology, medical oncology, radiation oncology, surgical oncology, and biostatistics. The main overall conclusions of the task force are ER is a strong predictor of response to endocrine therapy; ER status of all samples of invasive breast cancer or ductal carcinoma in situ (DCIS) should be evaluated by IHC; IHC measurements of PgR, although not as important clinically as ER, can provide useful information and should also be performed on all samples of invasive breast cancer or DCIS; IHC is the main testing strategy for evaluating ER and PgR in breast cancer and priority should be given to improve the quality of IHC testing methodologies; all laboratories performing IHC assays of ER and PgR should undertake formal validation studies to show both technical and clinical validation of the assay in use; and all laboratories performing IHC assays of hormone receptors in breast cancer should follow additional quality control and assurance measures as outlined in the upcoming guidelines from the American Society of Clinical Oncology and College of American Pathologists.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1

    Early Breast Cancer Trialists’ Collaborative Group. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365:16871717.

    • Search Google Scholar
    • Export Citation
  • 2

    Clarke M, Coates AS, Darby SC. Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer: patient-level meta-analysis of randomised trials. Lancet 2008;371:2940.

    • Search Google Scholar
    • Export Citation
  • 3

    Manni A, Arafah B, Pearson OH. Estrogen and progesterone receptors in the prediction of response of breast cancer to endocrine therapy. Cancer 1980;46(12 Suppl):28382841.

    • Search Google Scholar
    • Export Citation
  • 4

    Osborne CK, Yochmowitz MG, Knight WA III, McGuire WL. The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer 1980;46(12 Suppl):28842888.

    • Search Google Scholar
    • Export Citation
  • 5

    Viale G, Regan MM, Maiorano E. 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;26:14041410.

    • Search Google Scholar
    • Export Citation
  • 6

    Berry DA, Cirrincione C, Henderson IC. Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA 2006;295:16581667.

    • Search Google Scholar
    • Export Citation
  • 7

    Hede K. Breast cancer testing scandal shines spotlight on black box of clinical laboratory testing. J Natl Cancer Inst 2008;100:836837, 844.

    • Search Google Scholar
    • Export Citation
  • 8

    Allred DC. Commentary: hormone receptor testing in breast cancer: a distress signal from Canada. Oncologist 2008;13:11341136.

  • 9

    CBC News. Quebec re-examining breast cancer study. Available at: http://www.cbc.ca/health/story/2009/05/30/breast-cancer-quebec.html Accessed August 2, 2009.

    • Search Google Scholar
    • Export Citation
  • 10

    Rhodes A, Jasani B, Barnes DM. Reliability of immunohistochemical demonstration of oestrogen receptors in routine practice: interlaboratory variance in the sensitivity of detection and evaluation of scoring systems. J Clin Pathol 2000;53:125130.

    • Search Google Scholar
    • Export Citation
  • 11

    Viale G, Regan MM, Maiorano E. 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 2007;25:38463852.

    • Search Google Scholar
    • Export Citation
  • 12

    Badve SS, Baehner FL, Gray RP. 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;26:24732481.

    • Search Google Scholar
    • Export Citation
  • 13

    Nadji M, Gomez-Fernandez C, Ganjei-Azar P, Morales AR. Immunohistochemistry of estrogen and progesterone receptors reconsidered: experience with 5,993 breast cancers. Am J Clin Pathol 2005;123:2127.

    • Search Google Scholar
    • Export Citation
  • 14

    Elledge RM, Green S, Pugh R. Estrogen receptor (ER) and progesterone receptor (PgR), by LB 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 2000;89:111117.

    • Search Google Scholar
    • Export Citation
  • 15

    Rhodes A, Jasani B, Balaton AJ. Frequency of oestrogen and progesterone receptor positivity by immunohistochemistry analysis in 7016 breast carcinomas: correlation with patient age, assay sensitivity, threshold value, and mammographic screening. J Clin Oncol 2009;53:688696.

    • Search Google Scholar
    • Export Citation
  • 16

    Winn RJ, McClure JS. About the NCCN Clinical Practice Guidelines in Oncology. Available at: http://www.nccn.org/professionals/physician_gls/about.asp Accessed August 2, 2009.

    • Search Google Scholar
    • Export Citation
  • 17

    Jensen EV. On the mechanism of estrogen action. Perspect Biol Med 1962;6:4759.

  • 18

    Jensen EV, Jordan VC. The estrogen receptor: a model for molecular medicine. Clin Cancer Res 2003;9:19801989.

  • 19

    Greene GL, Press MF. Structure and dynamics of the estrogen receptor. J Steroid Biochem 1986;24:17.

  • 20

    Kuiper GG, Enmark E, Pelto-Huikko M. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S A 1996;93:59255930.

    • Search Google Scholar
    • Export Citation
  • 21

    Kuiper GG, Carlsson B, Grandien K. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 1997;138:863870.

    • Search Google Scholar
    • Export Citation
  • 22

    Enmark E, Pelto-Huikko M, Grandien K. Human estrogen receptor beta-gene structure, chromosomal localization, and expression pattern. J Clin Endocrinol Metab 1997;82:42584265.

    • Search Google Scholar
    • Export Citation
  • 23

    Horwitz KB, Alexander PS. In situ photolinked nuclear progesterone receptors of human breast cancer cells: subunit molecular weights after transformation and translocation. Endocrinology 1983;113:21952201.

    • Search Google Scholar
    • Export Citation
  • 24

    Kastner P, Krust A, Turcotte B. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. J Embo 1990;9:16031614.

    • Search Google Scholar
    • Export Citation
  • 25

    Ellmann S, Sticht H, Thiel F. Estrogen and progesterone receptors: from molecular structures to clinical targets. Cell Mol Life Sci 2009;66:24052426.

    • Search Google Scholar
    • Export Citation
  • 26

    Tanenbaum DM, Wang Y, Williams SP, Sigler PB. Crystallographic comparison of the estrogen and progesterone receptor’s ligand binding domains. Proc Natl Acad Sci U S A 1998;95:59986003.

    • Search Google Scholar
    • Export Citation
  • 27

    Figtree GA, McDonald D, Watkins H, Channon KM. Truncated estrogen receptor alpha 46-kDa isoform in human endothelial cells: relationship to acute activation of nitric oxide synthase. Circulation 2003;107:120126.

    • Search Google Scholar
    • Export Citation
  • 28

    Poola I, Speirs V. Expression of alternatively spliced estrogen receptor alpha mRNAs is increased in breast cancer tissues. J Steroid Biochem Mol Biol 2001;78:459469.

    • Search Google Scholar
    • Export Citation
  • 29

    Fasco MJ, Keyomarsi K, Arcaro KF, Gierthy JF. Expression of an estrogen receptor alpha variant protein in cell lines and tumors. Mol Cell Endocrinol 2000;166:156169.

    • Search Google Scholar
    • Export Citation
  • 30

    Pedram A, Razandi M, Levin ER. Nature of functional estrogen receptors at the plasma membrane. Mol Endocrinol 2006;20:19962009.

  • 31

    Schlegel A, Wang C, Katzenellenbogen BS. Caveolin-1 potentiates estrogen receptor alpha (ERalpha) signaling. caveolin-1 drives ligand-independent nuclear translocation and activation of ERalpha. J Biol Chem 1999;274:3355133556.

    • Search Google Scholar
    • Export Citation
  • 32

    Pedram A, Razandi M, Sainson RC. A conserved mechanism for steroid receptor translocation to the plasma membrane. J Biol Chem 2007;282:2227822288.

    • Search Google Scholar
    • Export Citation
  • 33

    Norman AW, Mizwicki MT, Norman DP. Steroid-hormone rapid actions, membrane receptors and a conformational ensemble model. Nat Rev Drug Discov 2004;3:2741.

    • Search Google Scholar
    • Export Citation
  • 34

    Levin ER, Pietras RJ. Estrogen receptors outside the nucleus in breast cancer. Breast Cancer Res Treat 2008;108:351361.

  • 35

    Likhite VS, Stossi F, Kim K. Kinase-specific phosphorylation of the estrogen receptor changes receptor interactions with ligand, deoxyribonucleic acid, and coregulators associated with alterations in estrogen and tamoxifen activity. Mol Endocrinol 2006;20:31203132.

    • Search Google Scholar
    • Export Citation
  • 36

    Mintz PJ, Habib NA, Jones LJ. The phosphorylated membrane estrogen receptor and cytoplasmic signaling and apoptosis proteins in human breast cancer. Cancer 2008;113:14891495.

    • Search Google Scholar
    • Export Citation
  • 37

    Giordano C, Cui Y, Barone I. Growth factor-induced resistance to tamoxifen is associated with a mutation of estrogen receptor alpha and its phosphorylation at serine 305. Breast Cancer Res Treat 2009; in press.

    • Search Google Scholar
    • Export Citation
  • 38

    Wijayaratne AL, McDonnell DP. The human estrogen receptor-alpha is a ubiquitinated protein whose stability is affected differentially by agonists, antagonists, and selective estrogen receptor modulators. J Biol Chem 2001;276:3568435692.

    • Search Google Scholar
    • Export Citation
  • 39

    Jordan VC, O’Malley BW. Selective estrogen-receptor modulators and antihormonal resistance in breast cancer. J Clin Oncol 2007;25:58155824.

    • Search Google Scholar
    • Export Citation
  • 40

    McClelland RA, Manning DL, Gee JM. Effects of short-term antiestrogen treatment of primary breast cancer on estrogen receptor mRNA and protein expression and on estrogen-regulated genes. Breast Cancer Res Treat 1996;41:3141.

    • Search Google Scholar
    • Export Citation
  • 41

    Pietras RJ. Biologic basis of sequential and combination therapies for hormone-responsive breast cancer. Oncologist 2006;11:704717.

  • 42

    Miller WR, Bartlett J, Brodie AM. Aromatase inhibitors: are there differences between steroidal and nonsteroidal aromatase inhibitors and do they matter? Oncologist 2008;13:829837.

    • Search Google Scholar
    • Export Citation
  • 43

    Normanno N, Di Maio M, De Maio E. Mechanisms of endocrine resistance and novel therapeutic strategies in breast cancer. Endocr Relat Cancer 2005;12:721747.

    • Search Google Scholar
    • Export Citation
  • 44

    Generali D, Buffa FM, Berruti A. Phosphorylated ERalpha, HIF-1alpha, and MAPK signaling as predictors of primary endocrine treatment response and resistance in patients with breast cancer. J Clin Oncol 2009;27:227234.

    • Search Google Scholar
    • Export Citation
  • 45

    Dowsett M, Allred C, Knox J. Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 (HER-2) status with recurrence in the Arimidex, Tamoxifen, Alone or in Combination trial. J Clin Oncol 2008;26:10591065.

    • Search Google Scholar
    • Export Citation
  • 46

    Pietras RJ, Arboleda J, Reese DM. HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone-independent growth in human breast cancer cells. Oncogene 1995;10:24352446.

    • Search Google Scholar
    • Export Citation
  • 47

    McGuire WL. Breast cancer prognostic factors: evaluation guidelines. J Natl Cancer Inst 1991;83:154155.

  • 48

    Burke HB, Henson DE. The American Joint Committee on Cancer. Criteria for prognostic factors and for an enhanced prognostic system. Cancer 1993;72:31313135.

    • Search Google Scholar
    • Export Citation
  • 49

    Henson DE, Fielding LP, Grignon DJ. College of American Pathologists Conference XXVI on clinical relevance of prognostic markers in solid tumors. Summary. Members of the Cancer Committee. Arch Pathol Lab Med 1995;119:11091112.

    • Search Google Scholar
    • Export Citation
  • 50

    Hayes DF, Bast RC, Desch CE. Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers. J Natl Cancer Inst 1996;88:14561466.

    • Search Google Scholar
    • Export Citation
  • 51

    Harris L, Fritsche H, Mennel R. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 2007;25:52875312.

    • Search Google Scholar
    • Export Citation
  • 52

    Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 1998;11:155168.

    • Search Google Scholar
    • Export Citation
  • 53

    Graham JD, Roman SD, McGowan E. Preferential stimulation of human progesterone receptor B expression by estrogen in T-47D human breast cancer cells. J Biol Chem 1995;270:3069330700.

    • Search Google Scholar
    • Export Citation
  • 54

    Wei LL, Krett NL, Francis MD. Multiple human progesterone receptor messenger ribonucleic acids and their autoregulation by progestin agonists and antagonists in breast cancer cells. Mol Endocrinol 1988;2:6272.

    • Search Google Scholar
    • Export Citation
  • 55

    McGuire WL. Estrogen receptors in human breast cancer. J Clin Invest 1973;52:7377.

  • 56

    Clark GM. Prognostic and predictive factors. In: Harris J, Lippman ME, Morrow M, Hellman S, eds. Diseases of the Breast. Philadelphia: Lippincott-Raven; 1996:461485.

    • Search Google Scholar
    • Export Citation
  • 57

    Osborne CK. Receptors. In: Harris JR, Hellman S, Henderson JC, eds. Philadelphia: Lippincott; 1991:310325.

  • 58

    McCarty KS Jr, Miller LS, Cox EB. Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med 1985;109:716721.

    • Search Google Scholar
    • Export Citation
  • 59

    McCarty KS Jr, Szabo E, Flowers JL. Use of a monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors. Cancer Res 1986;46(Suppl 8):4244s4248s.

    • Search Google Scholar
    • Export Citation
  • 60

    Magne N, Toillon RA, Castadot P. Different clinical impact of estradiol receptor determination according to the analytical method: a study on 1940 breast cancer patients over a period of 16 consecutive years. Breast Cancer Res Treat 2006;95:179184.

    • Search Google Scholar
    • Export Citation
  • 61

    Budwit-Novotny DA, McCarty KS, Cox EB. Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody. Cancer Res 1986;46:54195425.

    • Search Google Scholar
    • Export Citation
  • 62

    Dowsett M. Overexpression of HER-2 as a resistance mechanism to hormonal therapy for breast cancer. Endocr Relat Cancer 2001;8:191195.

    • Search Google Scholar
    • Export Citation
  • 63

    Collins LC, Botero ML, Schnitt SJ. Bimodal frequency distribution of estrogen receptor immunohistochemical staining results in breast cancer: an analysis of 825 cases. Am J Clin Pathol 2005;123:1620.

    • Search Google Scholar
    • Export Citation
  • 64

    Fisher ER, Anderson S, Dean S. Solving the dilemma of the immunohistochemical and other methods used for scoring estrogen receptor and progesterone receptor in patients with invasive breast carcinoma. Cancer 2005;103:164173.

    • Search Google Scholar
    • Export Citation
  • 65

    Turbin DA, Leung S, Cheang MC. Automated quantitative analysis of estrogen receptor expression in breast carcinoma does not differ from expert pathologist scoring: a tissue microarray study of 3484 cases. Breast Cancer Res Treat 2008;110:417426.

    • Search Google Scholar
    • Export Citation
  • 66

    Harvey JM, Clark GM, Osborne CK, Allred DC. 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;17:14741481.

    • Search Google Scholar
    • Export Citation
  • 67

    Barnes DM, Harris WH, Smith P. 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;74:14451451.

    • Search Google Scholar
    • Export Citation
  • 68

    Wilbur DC, Willis J, Mooney RA. Estrogen and progesterone receptor detection in archival formalin-fixed, paraffin-embedded tissue from breast carcinoma: a comparison of immunohistochemistry with the dextran-coated charcoal assay. Mod Pathol 1992;5:7984.

    • Search Google Scholar
    • Export Citation
  • 69

    Regan MM, Viale G, Mastropasqua MG. Re-evaluating adjuvant breast cancer trials: assessing hormone receptor status by immunohistochemical versus extraction assays. J Natl Cancer Inst 2006;98:15711581.

    • Search Google Scholar
    • Export Citation
  • 70

    Mohsin SK, Weiss H, Havighurst T. Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study. Mod Pathol 2004;17:15451554.

    • Search Google Scholar
    • Export Citation
  • 71

    Allred DC, Mohsin SK. The assessment of hormone receptors in breast cancer by immunohistochemistry. Semin Breast Dis 2005;8:5761.

  • 72

    Cheang MC, Treaba DO, Speers CH. Immunohistochemical detection using the new rabbit monoclonal antibody SP1 of estrogen receptor in breast cancer is superior to mouse monoclonal antibody 1D5 in predicting survival. J Clin Oncol 2006;24:56375644.

    • Search Google Scholar
    • Export Citation
  • 73

    Love RR, Duc NB, Allred DC. Oophorectomy and tamoxifen adjuvant therapy in premenopausal Vietnamese and Chinese women with operable breast cancer. J Clin Oncol 2002;20:25592566.

    • Search Google Scholar
    • Export Citation
  • 74

    Ellis MJ, Tao Y, Luo J. Outcome prediction for estrogen receptor-positive breast cancer based on postneoadjuvant endocrine therapy tumor characteristics. J Natl Cancer Inst 2008;100:13801388.

    • Search Google Scholar
    • Export Citation
  • 75

    Horiguchi J, Koibuchi Y, Iijima K. Co-expressed type of ER and HER2 protein as a predictive factor in determining resistance to antiestrogen therapy in patients with ER-positive and HER2-positive breast cancer. Oncol Rep 2005;14:11091116.

    • Search Google Scholar
    • Export Citation
  • 76

    Arpino G, Green SJ, Allred DC. HER-2 amplification, HER-1 expression, and tamoxifen response in estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group study. Clin Cancer Res 2004;10:56705676.

    • Search Google Scholar
    • Export Citation
  • 77

    ER/PR pharm DX™ kit [Package Insert]. Carpinteria, CA: Dako Corp, 2008.

  • 78

    Phillips T, Murray G, Wakamiya K. Development of standard estrogen and progesterone receptor immunohistochemical assays for selection of patients for antihormonal therapy. Appl Immunohistochem Mol Morphol 2007;15:325331.

    • Search Google Scholar
    • Export Citation
  • 79

    Chung GG, Zerkowski MP, Ghosh S. Quantitative analysis of estrogen receptor heterogeneity in breast cancer. Lab Invest 2007;87:662669.

  • 80

    Rimm DL, Giltnane JM, Moeder C. Bimodal population or pathologist artifact? J Clin Oncol 2007;25:24872488.

  • 81

    McCabe A, Dolled-Filhart M, Camp RL, Rimm DL. Automated quantitative analysis (AQUA) of in situ protein expression, antibody concentration, and prognosis. J Natl Cancer Inst 2005;97:18081815.

    • Search Google Scholar
    • Export Citation
  • 82

    Cregger M, Berger AJ, Rimm DL. Immunohistochemistry and quantitative analysis of protein expression. Arch Pathol Lab Med 2006;130:10261030.

  • 83

    Mina L, Soule SE, Badve S. Predicting response to primary chemotherapy: gene expression profiling of paraffin-embedded core biopsy tissue. Breast Cancer Res Treat 2007;103:197208.

    • Search Google Scholar
    • Export Citation
  • 84

    Paik S, Shak S, Tang G. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004;351:28172826.

    • Search Google Scholar
    • Export Citation
  • 85

    Paik S, Tang G, Shak S. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 2006;24:37263734.

    • Search Google Scholar
    • Export Citation
  • 86

    Allred DC. Problems and solutions in the evaluation of hormone receptors in breast cancer. J Clin Oncol 2008;26:24332435.

  • 87

    Roepman P, Horlings HM, Krijgsman O. Microarray-based readout of ER, PR, and HER2 expression in breast cancer tissue [abstract]. Presented at the 2008 ASCO Breast Cancer Symposium; September 5–7, 2008; Washington, DC. Abstract 33.

    • Search Google Scholar
    • Export Citation
  • 88

    Oh DS, Troester MA, Usary J. Estrogen-regulated genes predict survival in hormone receptor-positive breast cancers. J Clin Oncol 2006;24:16561664.

    • Search Google Scholar
    • Export Citation
  • 89

    Rakha EA, El-Sayed ME, Reis-Filho JS, Ellis IO. Expression profiling technology: its contribution to our understanding of breast cancer. Histopathology 2008;52:6781.

    • Search Google Scholar
    • Export Citation
  • 90

    Knight WA, Livingston RB, Gregory EJ, McGuire WL. Estrogen receptor as an independent prognostic factor for early recurrence in breast cancer. Cancer Res 1977;37:46694671.

    • Search Google Scholar
    • Export Citation
  • 91

    Fisher B, Redmond C, Fisher ER, Caplan R. Relative worth of estrogen or progesterone receptor and pathologic characteristics of differentiation as indicators of prognosis in node negative breast cancer patients: findings from National Surgical Adjuvant Breast and Bowel Project protocol B-06. J Clin Oncol 1988;6:10761087.

    • Search Google Scholar
    • Export Citation
  • 92

    Bardou VJ, Arpino G, Elledge RM. Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. J Clin Oncol 2003;21:19731979.

    • Search Google Scholar
    • Export Citation
  • 93

    Aamdal S, Bormer O, Jorgensen O. Estrogen receptors and long-term prognosis in breast cancer. Cancer 1984;53:25252529.

  • 94

    Hilsenbeck SG, Ravdin PM, de Moor CA. Time-dependence of hazard ratios for prognostic factors in primary breast cancer. Breast Cancer Res Treat 1998;52:227237.

    • Search Google Scholar
    • Export Citation
  • 95

    Pichon MF, Broet P, Magdelenat H. Prognostic value of steroid receptors after long-term follow-up of 2257 operable breast cancers. Br J Cancer 1996;73:15451551.

    • Search Google Scholar
    • Export Citation
  • 96

    Hahnel R, Woodings T, Vivian AB. Prognostic value of estrogen receptors in primary breast cancer. Cancer 1979;44:671675.

  • 97

    Saphner T, Tormey DC, Gray R. Annual hazard rates of recurrence for breast cancer after primary therapy. J Clin Oncol 1996;14:27382746.

  • 98

    Dunnwald LK, Rossing MA, Li CI. Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Res 2007;9:R6.

    • Search Google Scholar
    • Export Citation
  • 99

    Sorlie T, Perou CM, Tibshirani R. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001;98:1086910874.

    • Search Google Scholar
    • Export Citation
  • 100

    Sorlie T, Tibshirani R, Parker J. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci U S A 2003;100:84188423.

    • Search Google Scholar
    • Export Citation
  • 101

    Brenton JD, Carey LA, Ahmed AA, Caldas C. Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol 2005;23:73507360.

    • Search Google Scholar
    • Export Citation
  • 102

    Dawood S, Collins LC, Connolly JL. Defining breast cancer prognosis based on molecular phenotypes: results from a large cohort study [abstract]. Presented at the San Antonio Breast Cancer Symposium; December 10–14, 2008; San Antonio, Texas. Abstract 1068.

    • Search Google Scholar
    • Export Citation
  • 103

    Parker RL, Huntsman DG, Lesack DW. Assessment of interlaboratory variation in the immunohistochemical determination of estrogen receptor status using a breast cancer tissue microarray. Am J Clin Pathol 2002;117:723728.

    • Search Google Scholar
    • Export Citation
  • 104

    Cheang MC, Chia SK, Voduc D. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 2009;101:736750.

    • Search Google Scholar
    • Export Citation
  • 105

    Desmedt C, Haibe-Kains B, Wirapati P. Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin Cancer Res 2008;14:51585165.

    • Search Google Scholar
    • Export Citation
  • 106

    Hu Z, Fan C, Oh DS. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 2006;7:96.

  • 107

    Hugh J, Hanson J, Cheang MC. Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol 2009;27:11681176.

    • Search Google Scholar
    • Export Citation
  • 108

    Rouzier R, Perou CM, Symmans WF. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 2005;11:56785685.

    • Search Google Scholar
    • Export Citation
  • 109

    Srour N, Reymond MA, Steinert R. Lost in translation? A systematic database of gene expression in breast cancer. Pathobiology 2008;75:112118.

    • Search Google Scholar
    • Export Citation
  • 110

    Allred DC. The utility of conventional and molecular pathology in managing breast cancer. Breast Cancer Res 2008;10(Suppl 4):S4.

  • 111

    Livasy CA, Karaca G, Nanda R. Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol 2006;19:264271.

  • 112

    Allred DC, Wu Y, Mao S. Ductal carcinoma in situ and the emergence of diversity during breast cancer evolution. Clin Cancer Res 2008;14:370378.

    • Search Google Scholar
    • Export Citation
  • 113

    Livasy CA, Perou CM, Karaca G. Identification of a basal-like subtype of breast ductal carcinoma in situ. Hum Pathol 2007;38:197204.

  • 114

    Tamimi RM, Baer HJ, Marotti J. Comparison of molecular phenotypes of ductal carcinoma in situ and invasive breast cancer. Breast Cancer Res 2008;10:R67.

    • Search Google Scholar
    • Export Citation
  • 115

    Kok M, Linn S, van de Vijver M. Estrogen receptor phenotypes defined by gene expression profiling. In: Fuqua SAW, ed. Hormone Receptors in Breast Cancer. New York: Springer; 2009:231248.

    • Search Google Scholar
    • Export Citation
  • 116

    Allred DC, Bryant J, Land S. Estrogen receptor expression as a predictive marker of the effectiveness of tamoxifen in the treatment of DCIS: findings from NSABP protocol B-24 [abstract]. Breast Cancer Res Treat 2004;76(Suppl 1):Abstract 30.

    • Search Google Scholar
    • Export Citation
  • 117

    Goss PE, Ingle JN, Martino S. Efficacy of letrozole extended adjuvant therapy according to estrogen receptor and progesterone receptor status of the primary tumor: National Cancer Institute of Canada Clinical Trials Group MA.17. J Clin Oncol 2007;25:20062011.

    • Search Google Scholar
    • Export Citation
  • 118

    Ellis MJ, Coop A, Singh B. Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial. J Clin Oncol 2001;19:38083816.

    • Search Google Scholar
    • Export Citation
  • 119

    Fisher B, Redmond C, Brown A. Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project trial. J Clin Oncol 1986;4:459471.

    • Search Google Scholar
    • Export Citation
  • 120

    Hutchins LF, Green SJ, Ravdin PM. Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of Intergroup Protocol INT-0102. J Clin Oncol 2005;23:83138321.

    • Search Google Scholar
    • Export Citation
  • 121

    Adjuvant tamoxifen in the management of operable breast cancer: the Scottish Trial. Report from the Breast Cancer Trials Committee, Scottish Cancer Trials Office (MRC), Edinburgh. Lancet 1987;2:171175.

    • Search Google Scholar
    • Export Citation
  • 122

    Lippman ME, Allegra JC. Lack of estrogen receptor associated with an increased response rate to cytotoxic chemotherapy in metastatic breast cancer? Recent Results Cancer Res 1980;71:155161.

    • Search Google Scholar
    • Export Citation
  • 123

    U.S. Department of Health & Human Services, Nation Institutes of Health. NIH Consensus Development Program: Adjuvant Therapy for Breast Cancer. November 2000. Available at: http://consensus.nih.gov/2000/2000AdjuvantTherapyBreastCancer114html.htm Accessed August 2, 2009.

    • Search Google Scholar
    • Export Citation
  • 124

    Carlson RW, Allred DC, Anderson BO. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. J Natl Compr Canc Netw 2009;7:122192.

  • 125

    Albain K, Barlow W, O’Malley F. Concurrent (CAFT) versus sequential (CAF-T) chemohormonal therapy (cyclophosphamide, doxorubin, 5-fluorouracil, tamoxifen) versus T alone for postmenopausal node positive estrogen (ER) and/or progesterone (PgR) receptor-positive breast cancer: mature outcomes and new biologic correlates on phase III Intergroup trial 0100 [abstract]. Presented at the San Antonio Breast Cancer Symposium; December 8–11, 2004; San Antonio, Texas. Abstract LBA37.

    • Search Google Scholar
    • Export Citation
  • 126

    Goldhirsch A, Ingle JN, Gelber RD. Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2009. Ann Oncol 2009;20:13191329.

    • Search Google Scholar
    • Export Citation
  • 127

    Goldhirsch A, Wood WC, Gelber RD. Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007. Ann Oncol 2007;18:11331144.

    • Search Google Scholar
    • Export Citation
  • 128

    Simmons C, Miller N, Geddie D. Changes in tumor receptor status with time: a prospective study assessing the impact of obtaining confirmatory biopsy at metastatic recurrence on patient management [abstract]. Presented at the 2008 ASCO Breast Cancer Symposium; September 5–7, 2008; Washington, DC. Abstract 124.

    • Search Google Scholar
    • Export Citation
  • 129

    Guarneri V, Giovannelli S, Ficarra G. Comparison of HER-2 and hormone receptor expression in primary breast cancers and asynchronous paired metastases: impact on patient management. Oncologist 2008;13:838844.

    • Search Google Scholar
    • Export Citation
  • 130

    Broglio K, Moulder SL, Hsu L. Prognostic impact of discordance/concordance of triple-receptor expression between primary tumor and metastasis in patients with metastatic breast cancer [abstract]. J Clin Oncol 2008;26(Suppl 1):Abstract 1001.

    • Search Google Scholar
    • Export Citation
  • 131

    Zheng WQ, Lu J, Zheng JM. Variation of ER status between primary and metastatic breast cancer and relationship to p53 expression. Steroids 2001;66:905910.

    • Search Google Scholar
    • Export Citation
  • 132

    Rhodes A, Jasani B, Balaton AJ. Frequency of oestrogen and progesterone receptor positivity by immunohistochemical analysis in 7016 breast carcinomas: correlation with patient age, assay sensitivity, threshold value, and mammographic screening. J Clin Pathol 2000;53:688696.

    • Search Google Scholar
    • Export Citation
  • 133

    Rhodes A, Jasani B, Balaton AJ. Study of interlaboratory reliability and reproducibility of estrogen and progesterone receptor assays in Europe. Documentation of poor reliability and identification of insufficient microwave antigen retrieval time as a major contributory element of unreliable assays. Am J Clin Pathol 2001;115:4458.

    • Search Google Scholar
    • Export Citation
  • 134

    Chebil G, Bendahl PO, Idvall I, Ferno M. Comparison of immunohistochemical and biochemical assay of steroid receptors in primary breast cancer—clinical associations and reasons for discrepancies. Acta Oncol 2003;42:719725.

    • Search Google Scholar
    • Export Citation
  • 135

    Layfield LJ, Goldstein N, Perkinson KR, Proia AD. Interlaboratory variation in results from immunohistochemical assessment of estrogen receptor status. Breast J 2003;9:257259.

    • Search Google Scholar
    • Export Citation
  • 136

    Regitnig P, Reiner A, Dinges HP. Quality assurance for detection of estrogen and progesterone receptors by immunohistochemistry in Austrian pathology laboratories. Virchows Arch 2002;441:328334.

    • Search Google Scholar
    • Export Citation
  • 137

    Diaz LK, Sneige N. Estrogen receptor analysis for breast cancer: current issues and keys to increasing testing accuracy. Adv Anat Pathol 2005;12:1019.

    • Search Google Scholar
    • Export Citation
  • 138

    Taylor CR, Levenson RM. Quantification of immunohistochemistry—issues concerning methods, utility and semiquantitative assessment II. Histopathology 2006;49:411424.

    • Search Google Scholar
    • Export Citation
  • 139

    Yaziji H, Taylor CR, Goldstein NS. Consensus recommendations on estrogen receptor testing in breast cancer by immunohistochemistry. Appl Immunohistochem Mol Morphol 2008;16:513520.

    • Search Google Scholar
    • Export Citation
  • 140

    Walker RA. Immunohistochemical markers as predictive tools for breast cancer. J Clin Pathol 2008;61:689696.

  • 141

    Douglas-Jones AG, Collett N, Morgan JM, Jasani B. Comparison of core oestrogen receptor (ER) assay with excised tumour: intratumoral distribution of ER in breast carcinoma. J Clin Pathol 2001;54:951955.

    • Search Google Scholar
    • Export Citation
  • 142

    Park SY, Kim KS, Lee TG. The accuracy of preoperative core biopsy in determining histologic grade, hormone receptors, and human epidermal growth factor receptor 2 status in invasive breast cancer. Am J Surg 2009;197:266269.

    • Search Google Scholar
    • Export Citation
  • 143

    Gown AM. Current issues in ER and HER2 testing by IHC in breast cancer. Mod Pathol 2008;21(Suppl 2):S815.

  • 144

    Hodi Z, Chakrabarti J, Lee AH. The reliability of assessment of oestrogen receptor expression on needle core biopsy specimens of invasive carcinomas of the breast. J Clin Pathol 2007;60:299302.

    • Search Google Scholar
    • Export Citation
  • 145

    Nkoy FL, Hammond E, Rees W. Day of surgery affects estrogen receptor test results in women with breast cancer [abstract]. Presented at the San Antonio Breast Cancer Symposium; December 8–11, 2005; San Antonio, Texas. Abstract 5107.

    • Search Google Scholar
    • Export Citation
  • 146

    Goldstein NS, Ferkowicz M, Odish E. Minimum formalin fixation time for consistent estrogen receptor immunohistochemical staining of invasive breast carcinoma. Am J Clin Pathol 2003;120:8692.

    • Search Google Scholar
    • Export Citation
  • 147

    Rhodes A, Jasani B, Balaton AJ, Miller KD. Immunohistochemical demonstration of oestrogen and progesterone receptors: correlation of standards achieved on in house tumours with that achieved on external quality assessment material in over 150 laboratories from 26 countries. J Clin Pathol 2000;53:292301.

    • Search Google Scholar
    • Export Citation
  • 148

    Pertschuk LP, Masood S, Simone J. Estrogen receptor immunocytochemistry in endometrial carcinoma: a prognostic marker for survival. Gynecol Oncol 1996;63:2833.

    • Search Google Scholar
    • Export Citation
  • 149

    Gown AM. Unmasking the mysteries of antigen or epitope retrieval and formalin fixation. Am J Clin Pathol 2004;121:172174.

  • 150

    Riera J, Simpson JF, Tamayo R, Battifora H. Use of cultured cells as a control for quantitative immunocytochemical analysis of estrogen receptor in breast cancer. The Quicgel method. Am J Clin Pathol 1999;111:329335.

    • Search Google Scholar
    • Export Citation
  • 151

    Sompuram SR, Kodela V, Ramanathan H. Synthetic peptides identified from phage-displayed combinatorial libraries as immunodiagnostic assay surrogate quality-control targets. Clin Chem 2002;48:410420.

    • Search Google Scholar
    • Export Citation
  • 152

    Sompuram SR, Kodela V, Zhang K. A novel quality control slide for quantitative immunohistochemistry testing. J Histochem Cytochem 2002;50:14251434.

    • Search Google Scholar
    • Export Citation
  • 153

    Sompuram SR, Vani K, Bogen SA. A molecular model of antigen retrieval using a peptide array. Am J Clin Pathol 2006;125:9198.

  • 154

    Vani K, Sompuram SR, Fitzgibbons P, Bogen SA. National HER2 proficiency test results using standardized quantitative controls: characterization of laboratory failures. Arch Pathol Lab Med 2008;132:211216.

    • Search Google Scholar
    • Export Citation
  • 155

    Schnitt SJ. Estrogen receptor testing of breast cancer in current clinical practice: what’s the question? J Clin Oncol 2006;24:17971799.

    • Search Google Scholar
    • Export Citation
  • 156

    Umemura S, Itoh J, Itoh H. Immunohistochemical evaluation of hormone receptors in breast cancer: which scoring system is suitable for highly sensitive procedures? Appl Immunohistochem Mol Morphol 2004;12:813.

    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 602 226 21
PDF Downloads 372 209 22
EPUB Downloads 0 0 0