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Immunohistochemical assessment for estrogen receptor and progesterone receptor status in breast cancer: Analysis for a cut-off point as the predictor for endocrine therapy



An immunohistochemical (IHC) method is commonly used for determining estrogen receptor (ER) and progesterone receptor (PR) status in breast cancer. However, the proper cut-off points of IHC have not been established. Cut-off points for ER and PR status as predictive factors for endocrine therapy are needed.


A total of 249 cases of female breast cancer were enrolled. ER and PR status by IHC were analyzed using the proportion of stained cells and staining intensity by Allred’s score.


Proportion score (PS) and intensity score (IS) were related to enzyme immunoassay (EIA) titers, for both in ER and PR(p < 0.0001, all). PS correlated with IS in both ER and PR (R=0.47 and 0.41,respectively). ER status by IHC was related to tumor size and lymph node status, while PR was related to tumor size and menopausal status. In 152 patients who received endocrine therapy with a median follow-up term of 38 months, differences in disease-free survival were most significant using a cut-off point of PS 3 which indicated more than 10% of cells stained positively for both ER and PR(p = 0.0007 and 0.0087, respectively). In addition, combination analysis of ER and PR using this cut-off point revealed a notable prognostic difference.


A 10% staining proportion may be an acceptable cut-off point for both ER and PR status by IHC, in terms of predicting response to endocrine therapy in breast cancer.

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Estrogen receptor


Progesterone receptor


Hormone receptor


Enzyme immunoassay




Ligand-binding assay


Proportion score


Intensity score


Total score


  1. Shi SR, Key ME, Kalra KL: Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections.J Histochem Cytochem 39:741–748, 1991.

    PubMed  CAS  Google Scholar 

  2. Al Saati T, Clamens S, Cohen-Knafo E, Faye JC, Prats H, Coindre JM, Wafflart J, Caveriviere P, Bayard F, Delson G: Production of monoclonal antibodies to human estrogen-receptor protein (ER) using recombinant ER (RER).IntJ Cancer 55:651–654, 1993.

    Article  Google Scholar 

  3. Goulding H, Pinder S, Cannon R, Pearson D, Nicholson R, Snead D, Bell J, Elston CW, Robertoson JF, Blarney RW,et al: A new immunohistochemical antibody for the assessment of estrogen receptor status on routine formalin-fixed tissue samples.Hum Pathol 26:291–294, 1995.

    Article  PubMed  CAS  Google Scholar 

  4. Zofrani B, Aubriot M-H, Mouret E, de Cremoux P, de Rycke Y, Nicolas A, Boudou E, Vincent-Salomon A, Magdelenat H, Sastre-Garau X: High sensitivity and specificity of immunohistochemistry for the detection of hormone receptors in breast carcinoma: comparison with biochemical determination in a prospective study of 793 cases.Histopathol 37:536–545, 2000.

    Article  Google Scholar 

  5. Snead DRJ, Bell JA, Dion AR, Nicholson RI, Elston CW, Blarney RW, Ellis IO: Methodology of immunohistochemical detection of oestorogen receptor in human breast carcinoma in in formalin-fixed paraffin-embedded tissue: a comparison with frozen section methodology.Histopathol 23:233–238, 1993.

    Article  CAS  Google Scholar 

  6. Barnes DM, Millis RR, Beex LVAM, Thorpe SM, Leake RE: Increased use of immunohistchemistry for oestrogen receptor measurement in mammary carcinoma: the need for quality assurance.Eur J Cancer 34:1677–1682, 1998.

    Article  PubMed  CAS  Google Scholar 

  7. Rhodes A, Jasani B, Barnes D, Bobrow LG, Miller KD: The reliability of immunohistochemical demonstration of estrogen receptors in routine practice: interlaboratory variance in the sensitivity of detection and evaluation of scoring system.J Clin Pathol 53:125–130, 2000.

    Article  PubMed  CAS  Google Scholar 

  8. Barnes DM, Harris WH, Smith P, Millis RR, Rubens RD: Immunohistochemical determination of oestrogen receptor: comparision of differnce methods of assessment of staining and correlation with clinical outcome of breast cancer patients.Br J Cancer 74:1445–1451, 1996.

    PubMed  CAS  Google Scholar 

  9. Rhodes A, Jasani B, Balaton AJ, Barnes DM, Miller KD: 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 53:688–696, 2000.

    Article  PubMed  CAS  Google Scholar 

  10. Thike AA, Chng MJ, Fook-Chong S, Tan PH: immunohistochemical expression of hormone receptor in invasive breast carcinoma: correlation of results of H-score with pathological parameters.Pathol 33:21–25, 2001.

    CAS  Google Scholar 

  11. Jensen V, Andersen J: Value of immunohistochemical-determined estrogen receptor status and proliferative activity in breast cancer: a retrospective study including patients treated by endocrine therapy at the time of recurrence.Breast 5:127–134, 1996.

    Article  Google Scholar 

  12. Leake R: Prediction of hormone sensitivity-the receptor years and onwards.Endocrine-Related Cancer 4:289–296, 1997.

    Article  Google Scholar 

  13. Allred DC, Harvey JM, Berardo M, Clark GM: Prognostic and predictive factors in breast cancer by immunohistochemical analysis.Mod Pathol 11:155–168, 1998.

    PubMed  CAS  Google Scholar 

  14. Ferrero-Pous M, Trassard M, Doussal VL, Hacene K, Tubiana-Hulin M, Spyratos F: Comparison of enzyme immunoassay and immunohistochemical measurements of estrogen and progesterone receptors in breast cancer patients.Appl Immunohistochem Molecular Morphol 9:267–275, 2001.

    Article  CAS  Google Scholar 

  15. 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 17:1474–1481, 1999.

    PubMed  CAS  Google Scholar 

  16. Regitnig P, Reiner A, Dinges HP, Hoefler G, Muller HE, Lax SF, Obrist P, Rudas M, Quehenberger F: Quality assurance for detection of estrogen and progesterone receptors by immunohistochemistry in Austrian pathology laboratories.Virchows Archiv 441:328–334, 2002.

    Article  PubMed  CAS  Google Scholar 

  17. Early Breast Cancer Trialists’ Collaboration Group: Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy: 133 randomised trials involving 31000 recurrences and 24000 deaths among 75000 women.Lancet 339:1–15, 71-85, 1992.

    Google Scholar 

  18. Miles DW, Harris WH, Gillett CE, Smith P, Barnes DM: The effect of c-erbB2 and oestrogen receptor status on survival women with primary breast cancer treated with adjuvant CMF.Int J Cancer 84:354–359, 1999.

    Article  PubMed  CAS  Google Scholar 

  19. Barnes DM, Hanby AM: Oestrogen and progesterone receptors in breast cancer: past, present and feature.Histopathol 38:271–274, 2001.

    Article  CAS  Google Scholar 

  20. MacGrogan G, Soubeyran G, de Mascarel I: Immunohistochemical detection of progesterone receptors in breast invasive ductal carcinomas: a correlative study of 942 cases.Appl Immunohistochem 4:219–227, 1996.

    Google Scholar 

  21. Elledge RM, Osborne CK: Oestrogen receptors and breast cancer.Br Med J 314:1843–1844, 1997.

    CAS  Google Scholar 

  22. Clark GM, McGuire WL, Hubay CA, Pearson OH, Marshall JS: Progesterone receptors as a prognostic factor in stage II breast cancer.N Engl J Med 309:1343–1347, 1983.

    PubMed  CAS  Google Scholar 

  23. Thorpe SM, Rose C, Rasmussen BB, Mouridsen HT, Bayer T, Keiding N: Prognostic value of steroid hormone receptors: multivariate analysis of systemically untreated patients with node negative primary breast cancer.Cancer Res 47:6126–6133, 1987.

    PubMed  CAS  Google Scholar 

  24. Sunderland MC, McGuire WL: Hormones and breast cancer.Trends Endocrinol Metab 2:72–76, 1991.

    Article  PubMed  CAS  Google Scholar 

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Ogawa, Y., Moriya, T., Kato, Y. et al. 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 11, 267–275 (2004).

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Key words

  • Estrogen receptor
  • Progesterone receptor
  • Immunohistochemistry
  • Cut-off
  • Breast