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
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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.
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- Accepted May 11, 2006.
- Received February 2, 2006.
- Revision received April 28, 2006.