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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Prediction of fulvestrant efficacy in patients with advanced breast cancer : retrospective-prospective evaluation of the predictive potential of a multigene expression assay. / Christensen, Troels Dreier; Buhl, Anna Sofie Kappel; Christensen, Ib Jarle; Buhl, Ida Kappel; Balslev, Eva; Knoop, Ann S; Danø, Hella; Glavicic, Vesna; Luczak, Adam; Langkjer, Sven Tyge; Linnet, Søren; Jakobsen, Erik Hugger; Bogovic, Jurij; Ejlertsen, Bent; Rasmussen, Annie; Hansen, Anker; Knudsen, Steen; Jensen, Peter Buhl; Nielsen, Dorte.
In: Breast Cancer, Vol. 27, No. 2, 03.2020, p. 266-276.Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review
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TY - JOUR
T1 - Prediction of fulvestrant efficacy in patients with advanced breast cancer
T2 - retrospective-prospective evaluation of the predictive potential of a multigene expression assay
AU - Christensen, Troels Dreier
AU - Buhl, Anna Sofie Kappel
AU - Christensen, Ib Jarle
AU - Buhl, Ida Kappel
AU - Balslev, Eva
AU - Knoop, Ann S
AU - Danø, Hella
AU - Glavicic, Vesna
AU - Luczak, Adam
AU - Langkjer, Sven Tyge
AU - Linnet, Søren
AU - Jakobsen, Erik Hugger
AU - Bogovic, Jurij
AU - Ejlertsen, Bent
AU - Rasmussen, Annie
AU - Hansen, Anker
AU - Knudsen, Steen
AU - Jensen, Peter Buhl
AU - Nielsen, Dorte
PY - 2020/3
Y1 - 2020/3
N2 - 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.
AB - 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.
KW - Advanced breast cancer
KW - Biomarker
KW - Fulvestrant
KW - Messenger RNA
KW - BIOMARKERS
KW - TRIAL
KW - THERAPY
KW - DOUBLE-BLIND
KW - COMBINATION
KW - POSTMENOPAUSAL WOMEN
KW - 500 MG
KW - AMERICAN SOCIETY
U2 - 10.1007/s12282-019-01017-7
DO - 10.1007/s12282-019-01017-7
M3 - Journal article
C2 - 31654283
VL - 27
SP - 266
EP - 276
JO - NPJ Breast Cancer
JF - NPJ Breast Cancer
SN - 2374-4677
IS - 2
ER -