Originally published as JCO Early Release 10.1200/JCO.2007.12.2747 on September 17 2007

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Biologic and Clinical Characteristics of Breast Cancer With Single Hormone Receptor–Positive Phenotype

Emad A. Rakha, Maysa E. El-Sayed, Andrew R. Green, E. Claire Paish, Desmond G. Powe, Julia Gee, Robert I. Nicholson, Andrew H.S. Lee, John F.R. Robertson, Ian O. Ellis

From the Department of Histopathology and Surgery, School of Molecular Medical Sciences, Nottingham University Hospitals National Health Service Trust and University of Nottingham, Nottingham, and Welsh School of Pharmacy, Cardiff University, Cardiff, United Kingdom

Address reprint requests to Emad Rakha, MD, PhD, Molecular Medical Sciences, University of Nottingham, Department of Histopathology, Nottingham City Hospital National Health Service Trust, Hucknall Road, Nottingham, NG5 1PB, United Kingdom; e-mail: emadrakha{at}yahoo.com

Purpose Response to endocrine therapy in breast cancer correlates with estrogen receptor (ER) and progesterone receptor (PgR) status. It is usually easier to decide treatment strategies in cases of double-positive/-negative phenotypes than in single-positive tumors.

Patients and Methods We have examined a large and well-characterized series of primary invasive breast carcinoma (1,944 cases) with long-term clinical follow-up and hormone therapy data. Patients were stratified according to ER and PgR expression and the study was focused on the single-positive groups (ER–/PgR+ and ER+/PgR–), to assess their main features and evaluate any prognostic and predictive difference between them and compare them with the double-positive/-negative tumors.

Results ER+/PgR–tumors were found more frequently in elderly, postmenopausal women. The majority were grade 2 ductal/no specific type carcinomas. There was no difference between the two groups with regard to lymph node stage. Survival analyses showed no difference between the two groups in terms of disease-free interval and overall survival. However, when compared with the double-negative phenotype, ER+/PgR–showed an association with better outcome but no such survival advantage was detected in case of ER–/PgR+ tumors. In the group of patients with ER+ tumors who received adjuvant hormonal therapy, absence of PgR (ER+/PgR–) was an independent predictor of development of recurrence and shorter survival and, hence, poorer response to hormonal therapy.

Conclusion ER+/PgR–and ER–/PgR+ tumors are biologically and clinically distinct groups of breast cancer that may require different treatment strategies with ER–/PgR+ exhibiting more aggressive behavioral characteristics.

published online ahead of print at www.jco.org on September 17, 2007.

This research was approved by Nottingham Research Ethics Committee 2 under the title of "Development of a Molecular Genetic Classification of Breast Cancer."

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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