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Imaging, Diagnosis, Prognosis

High Progesterone Receptor Expression Correlates to the Effect of Adjuvant Tamoxifen in Premenopausal Breast Cancer Patients

Maria Stendahl, Lisa Rydén, Bo Nordenskjöld, Per Ebbe Jönsson, Göran Landberg and Karin Jirström
Maria Stendahl
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Lisa Rydén
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Bo Nordenskjöld
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Per Ebbe Jönsson
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Göran Landberg
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Karin Jirström
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DOI: 10.1158/1078-0432.CCR-06-0248 Published August 2006
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Abstract

Purpose: Tamoxifen has long been the drug of choice in adjuvant endocrine therapy of steroid hormone receptor–positive breast cancer, and it still remains important due to its well-documented beneficial effect. Hormone receptor status is often reported as “positive” or “negative” using 10% positive nuclei as a cutoff. In this study, we aimed to assess whether a further subclassification of hormone receptor status could enhance the treatment predictive value.

Experimental Design: The immunohistochemical expression of estrogen receptor (ER) and progesterone receptor (PR) was quantified in tissue microarrays with tumors from 500 premenopausal breast cancer patients previously included in a randomized trial of adjuvant tamoxifen compared with an untreated control group.

Results: Our findings show a gradually increasing tamoxifen effect in tumors with >10% ER-positive nuclei. However, when analyzing tamoxifen response according to various PR fractions, we found that it was primarily patients with tumors showing >75% PR-positive nuclei that responded to tamoxifen treatment, with an improved recurrence-free [relative risk, 0.42 (0.25-0.70); P = 0.001] as well as overall [relative risk, 0.49 (0.28-0.84); P = 0.010] survival.

Conclusions: Adjuvant tamoxifen improved recurrence-free and overall survival for premenopausal patients with tumors showing >75% PR-positive nuclei. No effect could be shown in tumors with fewer PR-positive nuclei. The PR was a stronger predictor of treatment response than the ER. Based on these findings, we suggest the implementation of a fractioned rather than dichotomized immunohistochemical evaluation of hormone receptors in clinical practice, possibly with greater emphasis on the PR than the ER.

  • breast cancer
  • ER
  • PR
  • premenopausal
  • tamoxifen response

Footnotes

  • Grant support: The Swedish Cancer Society, Swegene/Wallenberg Consortium North, Lund University Research Funds, Malmö University Hospital Research and Cancer Funds, and Jönköping Regional Hospital Research Funds.

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted May 11, 2006.
    • Received February 2, 2006.
    • Revision received April 28, 2006.
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Clinical Cancer Research: 12 (15)
August 2006
Volume 12, Issue 15
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High Progesterone Receptor Expression Correlates to the Effect of Adjuvant Tamoxifen in Premenopausal Breast Cancer Patients
Maria Stendahl, Lisa Rydén, Bo Nordenskjöld, Per Ebbe Jönsson, Göran Landberg and Karin Jirström
Clin Cancer Res August 1 2006 (12) (15) 4614-4618; DOI: 10.1158/1078-0432.CCR-06-0248

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High Progesterone Receptor Expression Correlates to the Effect of Adjuvant Tamoxifen in Premenopausal Breast Cancer Patients
Maria Stendahl, Lisa Rydén, Bo Nordenskjöld, Per Ebbe Jönsson, Göran Landberg and Karin Jirström
Clin Cancer Res August 1 2006 (12) (15) 4614-4618; DOI: 10.1158/1078-0432.CCR-06-0248
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Clinical Cancer Research
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