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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Troels Dreier Christensen, University of Copenhagen
  • ,
  • Anna Sofie Kappel Buhl, Oncology Venture, Hoersholm, Denmark., University of Copenhagen
  • ,
  • Ib Jarle Christensen, University of Copenhagen
  • ,
  • Ida Kappel Buhl, University of Copenhagen, Oncology Venture, Hoersholm, Denmark.
  • ,
  • Eva Balslev, University of Copenhagen
  • ,
  • Ann S Knoop, University of Copenhagen
  • ,
  • Hella Danø, University of Copenhagen
  • ,
  • Vesna Glavicic, University of Copenhagen
  • ,
  • Adam Luczak, Aalborg University
  • ,
  • Sven Tyge Langkjer
  • Søren Linnet, Regionshospitalet Herning
  • ,
  • Erik Hugger Jakobsen, Vejle Sygehus
  • ,
  • Jurij Bogovic, Hospital of Southern Jutland
  • ,
  • Bent Ejlertsen, University of Copenhagen
  • ,
  • Annie Rasmussen, Oncology Venture, Hoersholm, Denmark.
  • ,
  • Anker Hansen, Oncology Venture, Hoersholm, Denmark.
  • ,
  • Steen Knudsen, Oncology Venture, Hoersholm, Denmark.
  • ,
  • Peter Buhl Jensen, Oncology Venture, Hoersholm, Denmark.
  • ,
  • Dorte Nielsen, University of Copenhagen

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.

Original languageEnglish
JournalBreast Cancer
Volume27
Issue2
Pages (from-to)266-276
Number of pages11
ISSN1340-6868
DOIs
Publication statusPublished - Mar 2020

    Research areas

  • Advanced breast cancer, Biomarker, Fulvestrant, Messenger RNA, BIOMARKERS, TRIAL, THERAPY, DOUBLE-BLIND, COMBINATION, POSTMENOPAUSAL WOMEN, 500 MG, AMERICAN SOCIETY

See relations at Aarhus University Citationformats

ID: 178009272