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Annals of Oncology Advance Access originally published online on February 23, 2006
Annals of Oncology 2006 17(5):818-826; doi:10.1093/annonc/mdl016
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© 2006 European Society for Medical Oncology

Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according oestrogen receptor, progesterone receptor, EGF receptor and HER2 status

M. Dowsett1,*, J. Houghton2, C. Iden2, J. Salter1, J. Farndon3, R. A'Hern4, R. Sainsbury5 and M. Baum6

1 Academic Department of Biochemistry, The Royal Marsden NHS Trust, London; 2 Clinical Trials Group of the Department of Surgery, Royal Free and University College Medical School, University College London, London; 3 University Department of Surgery, Bristol Royal Infirmary, Bristol; 4 Clinical Trials and Statistics Unit, Institute of Cancer Research, Sutton, Surrey; 5 Department of Surgery, University College, London; 6 The Portland Hospital, London, UK

* Correspondence to: Dr M. Dowsett, Academic Department of Biochemistry, The Royal Marsden NHS Trust, Fulham Road, London SW3 6JJ, UK. Tel: +44 (0)20 7808 2887; Fax: +44 (0)20 7376 3918; E-mail: mitch{at}icr.ac.uk

Background: Most women with oestrogen receptor (ER) positive primary breast cancer receive adjuvant tamoxifen after surgery. The measurement of tumour biomarkers should allow better selection of patients for such treatment or for therapies such as aromatase inhibitors.

Patients and methods: Histopathological blocks of primary breast cancer patients who had been randomized to receive 2-years tamoxifen or no adjuvant therapy in two mature randomised clinical trials were retrieved. Immunohistochemical staining for ER, progesterone receptor (PgR), HER2 and epidermal growth factor receptor (EGFR) was undertaken. The primary endpoint was relapse free survival.

Results: 813 patients were included in the study. Benefit from tamoxifen was seen in ER-positive patients [Relative risk (rr) 0.77, ci 0.63–0.93]. ER-negative patients also showed a strong trend to benefit from tamoxifen (rr 0.73, ci 0.52–1.02) which was largely confined to the PgR-positive group. Amongst the ER-positive group, PgR-positive and PgR-negative patients showed similar benefit (rr 0.81; ci 0.65–1.02 and 0.70; ci 0.49–0.99, respectively). Patients positive for HER2 did not benefit significantly (rr 1.14; ci 0.75–1.73) but this group was small.

Conclusions: Measurement of PgR status in ER-negative patients defines a group of patients that benefit from tamoxifen but would be excluded from tamoxifen therapy on the basis of ER status alone. The data are consistent with HER2 positive tumours being resistant to tamoxifen.

Key words: early breast cancer, tamoxifen, ER, PgR, EGFR, HER2


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