Breast Cancer Research and Treatment

, Volume 126, Issue 2, pp 421–430 | Cite as

Immunohistochemistry compared to cytosol assays for determination of estrogen receptor and prediction of the long-term effect of adjuvant tamoxifen

  • Mahmoud R. KhoshnoudEmail author
  • Britta Löfdahl
  • Helena Fohlin
  • Tommy Fornander
  • Olle Stål
  • Lambert Skoog
  • Jonas Bergh
  • Bo Nordenskjöld
Clinical trial


The purpose of this study is to compare immunohistochemistry (IHC) and cytosol-based assays for determination of estrogen receptor (ER) and prediction of response to adjuvant tamoxifen treatment in postmenopausal women with early-stage invasive breast cancer. The Stockholm Breast Cancer Study Group conducted a randomized trial during 1976 through 1990 comparing adjuvant tamoxifen versus control. The patients were stratified according to tumor size and lymph node status in high-risk and low-risk groups. In this study we evaluated 683 patients with “low risk” breast cancer (size ≤30 mm, lymph node-negative) for whom ER status had been determined by both the cytosol assays and IHC at one pathology laboratory. The median follow-up was 17 years. Six hundred eighty-three patients had tumors with ER determined by both methods, 536 (78.5%) were ER-positive by cytosol assays using the cutoff level at ≥0.05 fmol/μg DNA and 539 patients were ER-positive (79%) by IHC using the cutoff level at ≥10% cell stained. Thirty-nine tumors (5.7%) were ER-positive by cytosol but not by IHC, whereas the opposite pattern was found for 42 cases (6.1%). Only seven tumors had stained cells between 0 and 9% by IHC. The concordance between IHC and cytosol assays was high (88%). The kappa statistic was 0.65, 95% CI 0.58–0.72. Among patients classified as ER-negative no therapeutic benefit from tamoxifen was observed. Among patients with ER-expressing tumors, tamoxifen resulted in significantly better recurrence-free survival irrespective of the method (IHC: HR, 0.53, P < 0.001; cytosol: HR, 0.53, P < 0.001). The effect on overall survival was not statistically significant probably due to the limited sample size. Both IHC and cytosol assay accurately predict long-term response to adjuvant tamoxifen.


Breast cancer Estrogen receptor Tamoxifen Cytosol Immunohistochemical 



This research was supported by grants from the Swedish Cancer Society and the Swedish Research Council to Olle Stål and Jonas Bergh and funds of Jonas Bergh’s Research Group at Radiumhemmet and the Stockholm County Council.


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Mahmoud R. Khoshnoud
    • 1
    Email author
  • Britta Löfdahl
    • 2
  • Helena Fohlin
    • 3
  • Tommy Fornander
    • 1
  • Olle Stål
    • 4
  • Lambert Skoog
    • 5
  • Jonas Bergh
    • 6
    • 7
  • Bo Nordenskjöld
    • 4
  1. 1.Department of Oncology, Karolinska University HospitalKarolinska InstituteStockholmSweden
  2. 2.Department of PathologyUppsala University HospitalUppsalaSweden
  3. 3.Oncology CentreLinköping University HospitalLinköpingSweden
  4. 4.Department of Clinical and Experimental Medicine/Oncology, Faculty of Health SciencesLinköping UniversityLinköpingSweden
  5. 5.Department of Pathology, Karolinska University HospitalKarolinska InstituteStockholmSweden
  6. 6.Cancer Center KarolinskaKarolinska InstituteStockholmSweden
  7. 7.Medical Breast Unit, Christie HospitalPaterson Institute/Manchester UniversityManchesterUK

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