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01-03-2020 | Breast Cancer | Original Article

Prediction of fulvestrant efficacy in patients with advanced breast cancer: retrospective-prospective evaluation of the predictive potential of a multigene expression assay

Authors: Troels Dreier Christensen, Anna Sofie Kappel Buhl, Ib Jarle Christensen, Ida Kappel Buhl, Eva Balslev, Ann S. Knoop, Hella Danø, Vesna Glavicic, Adam Luczak, Sven Tyge Langkjer, Søren Linnet, Erik Hugger Jakobsen, Jurij Bogovic, Bent Ejlertsen, Annie Rasmussen, Anker Hansen, Steen Knudsen, Peter Buhl Jensen, Dorte Nielsen

Published in: Breast Cancer | Issue 2/2020

Abstract

Background

Fulvestrant is a selective oestrogen receptor (ER) degrader used as monotherapy and combination therapy for ER positive HER2 negative advanced breast cancer (ABC) in postmenopausal women. The drug response predictor (DRP), is a mathematical algorithm based on the expression of multiple genes in the tumour. The fulvestrant DRP algorithm has previously shown effect in BC. In this study, we investigated the DRP’s potential in predicting fulvestrant benefit.

Method

Among 695 patients with ABC prospectively included in a Danish Breast Cancer Cooperative Group (DBCG) cohort we retrospectively included 226 patients who received fulvestrant as monotherapy. The DRP result was based on mRNA extracted from tumour biopsies and analysed using Affymetrix array. Primary endpoint was time to progression (TTP).

Results

For patients who received fulvestrant in line one to four and were previously unexposed to adjuvant endocrine therapy, we identified a hazard ratio (HR) of 0.44 (90% confidence interval (90% CI) upper limit of 1.08, one sided p = 0.066) for a predicted positive vs negative outcome. A weaker association was seen when including patients exposed to adjuvant endocrine treatment or received fulvestrant in fifth or later lines. Exploratory analyses showed that the DRP was efficient when using recent biopsies for DRP estimate and among recently treated patients.

Conclusion

The DRP showed a potential in predicting fulvestrant treatment but was not significant in the overall analysis. Use of older biopsies, long-term endocrine treatment and multiple therapies between biopsy used for analysis and fulvestrant treatment, probably affect the predictive accuracy.

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Title: Prediction of fulvestrant efficacy in patients with advanced breast cancer: retrospective-prospective evaluation of the predictive potential of a multigene expression assay
Authors: Troels Dreier Christensen
Anna Sofie Kappel Buhl
Ib Jarle Christensen
Ida Kappel Buhl
Eva Balslev
Ann S. Knoop
Hella Danø
Vesna Glavicic
Adam Luczak
Sven Tyge Langkjer
Søren Linnet
Erik Hugger Jakobsen
Jurij Bogovic
Bent Ejlertsen
Annie Rasmussen
Anker Hansen
Steen Knudsen
Peter Buhl Jensen
Dorte Nielsen
Publication date: 01-03-2020
Publisher: Springer Japan
Keywords: Breast Cancer
Breast Cancer
Fulvestrant
Biomarkers
Published in: Breast Cancer / Issue 2/2020
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI: https://doi.org/10.1007/s12282-019-01017-7

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