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

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DOI

  • Troels Dreier Christensen, Københavns Universitet
  • ,
  • Anna Sofie Kappel Buhl, Oncology Venture, Hoersholm, Denmark., Københavns Universitet
  • ,
  • Ib Jarle Christensen, Københavns Universitet
  • ,
  • Ida Kappel Buhl, Københavns Universitet, Oncology Venture, Hoersholm, Denmark.
  • ,
  • Eva Balslev, Københavns Universitet
  • ,
  • Ann S Knoop, Københavns Universitet
  • ,
  • Hella Danø, Københavns Universitet
  • ,
  • Vesna Glavicic, Københavns Universitet
  • ,
  • Adam Luczak, Aalborg Universitet
  • ,
  • Sven Tyge Langkjer
  • Søren Linnet, Regionshospitalet Herning
  • ,
  • Erik Hugger Jakobsen, Vejle Sygehus
  • ,
  • Jurij Bogovic, Hospital of Southern Jutland
  • ,
  • Bent Ejlertsen, Københavns Universitet
  • ,
  • 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, Københavns Universitet

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.

OriginalsprogEngelsk
TidsskriftBreast Cancer
Vol/bind27
Nummer2
Sider (fra-til)266-276
Antal sider11
ISSN1340-6868
DOI
StatusUdgivet - mar. 2020

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