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

Authors' Affiliations: ¹ Department of Laboratory Medicine, Division of Pathology, Malmö University Hospital, Lund University, Malmö, Sweden; ² Department of Medicine, Ryhov Regional Hospital, Jönköping, Sweden; ³ Department of Oncology, University Hospital, Linköping, Sweden; and ⁴ Department of Surgery, Helsingborg Hospital, Helsingborg, Sweden

Requests for reprints: Karin Jirström, Division of Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, S-205 02 Malmö, Sweden. Phone: 46-40-333088; Fax: 46-40-337063; E-mail: karin.jirstrom{at}med.lu.se.

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.

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