Originally published as JCO Early Release 10.1200/JCO.2007.12.9437 on January 28 2008

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Relationship Between Quantitative Estrogen and Progesterone Receptor Expression and Human Epidermal Growth Factor Receptor 2 (HER-2) Status With Recurrence in the Arimidex, Tamoxifen, Alone or in Combination Trial

Mitch Dowsett, Craig Allred, Jill Knox, Emma Quinn, Janine Salter, Chris Wale, Jack Cuzick, Joan Houghton, Norman Williams, Elizabeth Mallon, Hugh Bishop, Ian Ellis, Denis Larsimont, Hironobu Sasano, Pauline Carder, Antonio Llombart Cussac, Fiona Knox, Valerie Speirs, John Forbes, Aman Buzdar

From the Academic Department of Biochemistry, Royal Marsden Hospital; Departments of Epidemiology and Mathematics & Statistics, Cancer Research UK, Wolfson Institute of Preventive Medicine; Clinical Trials Group, Department of Surgery, University College London, London; Department of Pathology, The Western Infirmary, Glasgow; Department of Surgery, The Royal Bolton Hospital, Bolton; Department of Histopathology, Nottingham University, Nottingham City Hospital, Nottingham; Bradford Teaching Hospitals NHS Foundation Trust, Bradford Royal Infirmary, Bradford; Wythenshawe Hospital, Wythenshawe, Manchester; Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, United Kingdom; Department of Pathology & Immunology, Washington University School of Medicine, St Louis, MO; Department of Pathology, Translational Research Unit, Institut Jules Bordet, Brussels, Belgium; Department of Pathology, Tohoku University School of Medicine, Sendai, Japan; Medical Oncology Service, Hospital Universitario Arnau Vilanova, Lleida, Spain; Department of Surgical Oncology, University of Newcastle, Newcastle Mater Hospital, New South Wales, Australia; and the Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX

Corresponding author: Mitch Dowsett, MD, Academic Department of Biochemistry, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, United Kingdom; e-mail: mitch.dowsett{at}icr.ac.uk

Purpose To determine the relationship between quantitative estrogen-receptor (ER) and progesterone-receptor (PgR) expression and human epidermal growth factor 2 (HER-2) status with time to recurrence (TTR) in postmenopausal women with hormone receptor–positive primary breast cancer treated with anastrozole or tamoxifen as adjuvant therapy.

Patients and Methods Formalin-fixed, paraffin-embedded tumor blocks were retrospectively collected from patients in the monotherapy arms of the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial and centrally tested for ER, PgR and HER-2. ER and PgR were scored using continuous scales and HER-2 was scored as 0 to 3+ with 2+ cases being analyzed by fluorescence in situ hybridization.

Results Blocks were collected from 2,006 of 5,880 eligible patients. Tissue was assessable and ER and/or PgR positivity confirmed centrally in 1,782 cases. In these, TTR was longer for anastrozole than for tamoxifen by a similar extent to that in the overall trial. None of the three biomarkers identified a set of patients with differential benefit from anastrozole over tamoxifen. Patients with low ER, low PgR, and high HER-2 expression had a poorer prognosis with either drug. Only 2.6% of patients in the highest quartile of PgR experienced recurrence after 5 years, compared with 13.2% in the lowest quartile.

Conclusion Quantitative expression of ER and PgR and HER-2 status did not identify patients with differential relative benefit from anastrozole over tamoxifen: TTR was longer for anastrozole than for tamoxifen in all molecular subgroups. Low ER or PgR or high HER-2 expression are associated with a high risk of recurrence with either anastrozole or tamoxifen.

Supported by Breakthrough Breast Cancer, AstraZeneca, and the Royal Marsden Hospital.

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

published online ahead of print at www.jco.org on January 28, 2008.

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