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Open Access Research article

A randomized trial to assess the biological activity of short-term (pre-surgical) fulvestrant 500 mg plus anastrozole versus fulvestrant 500 mg alone or anastrozole alone on primary breast cancer

John FR Robertson1*, J Michael Dixon2, D Mark Sibbering3, Ali Jahan4, Ian O Ellis5, Eddie Channon6, Pauline Hyman-Taylor1, Robert I Nicholson7 and Julia MW Gee7

Author Affiliations

1 Graduate Entry Medicine and Health School (GEMS), University of Nottingham, Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3DT, UK

2 Breast Unit, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU, UK

3 Breast Unit, Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3DT, UK

4 Division of Surgery, Kingsmill Hospital, Mansfield Road, Sutton-in-Ashfield, NG17 4JL, UK

5 School of Molecular Medicine, A Floor, West Block Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK

6 Chirostat Statistical Consulting, University Boulevard, Beeston, Nottingham, NG9 2GJ, UK

7 School of Pharmacy and Pharmaceutical Sciences, Redwood Building, King Edward VII Avenue, Cardiff University, Cardiff, CF10 3NB, UK

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Breast Cancer Research 2013, 15:R18  doi:10.1186/bcr3393

Published: 5 March 2013

Abstract

Introduction

Fulvestrant shows dose-dependent biological activity. Greater estrogen-receptor (ER) blockade may feasibly be achieved by combining fulvestrant with anastrozole. This pre-surgical study compared fulvestrant plus anastrozole versus either agent alone in patients with ER-positive breast cancer.

Methods

In this double-blind, multicenter trial, 121 patients received fulvestrant 500 mg on Day 1 plus anastrozole 1 mg/day for 14 to 21 days (F + A); fulvestrant plus anastrozole placebo (F); or fulvestrant placebo plus anastrozole (A), 2 to 3 weeks before surgery. ER, progesterone-receptor (PgR) and Ki67 expression were determined from tumor biopsies before treatment and at surgery.

Results

A total of 103 paired samples were available (F, n = 35; F+A, n = 31; A, n = 37). All treatments significantly reduced mean ER expression from baseline (F: -41%, P = 0.0001; F + A: -39%, P = 0.0001; A: -13%, P = 0.0034). F and F + A led to greater reductions in ER versus A (both P = 0.0001); F + A did not lead to additional reductions versus F. PgR and Ki67 expression were significantly reduced with all treatments (means were -34% to -45%, and -75% to -85%, respectively; all P = 0.0001), with no differences between groups.

Conclusions

In this short-term study, all treatments reduced ER expression, although F and F + A showed greater reductions than A. No significant differences were detected between the treatment groups in terms of PgR and Ki67 expression. No additional reduction in tumor biomarkers with combination treatment was observed, suggesting that F + A is unlikely to have further clinical benefit over F alone.

Trial registration

Clinicaltrials.gov NCT00259090.