Prediction of exemestane benefit in patients with advanced breast cancer based on diagnostic biopsy mRNA analysis
| Autor: | Knud Mejer Nelausen, Vesna Glavicic, Anna Sofie Kappel Buhl, Steen Knudsen, Soeren Linnet, Sven Tyge Langkjer, Troels Dreier Christensen, Peter Buhl Jensen, Adam Luczak, AS Knoop, Dorte Nielsen, Eva Harder Brix, Jurij Bogovic, Eva Balslev, Ulla Hald Buhl, Iben Kümler, Bent Ejlertsen, Erik Jakobsen, Ib Jarle Christensen, Peter Michael Vestlev |
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| Rok vydání: | 2017 |
| Předmět: |
Gynecology
Oncology Cancer Research medicine.medical_specialty Messenger RNA medicine.diagnostic_test business.industry Advanced breast medicine.medical_treatment Estrogen receptor Cancer medicine.disease chemistry.chemical_compound Exemestane chemistry Internal medicine Biopsy medicine business Adjuvant Steroidal Aromatase Inhibitor |
| Zdroj: | Journal of Clinical Oncology. 35:e12532-e12532 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2017.35.15_suppl.e12532 |
| Popis: | e12532 Background: Exemestaneis a steroidal aromatase inhibitor used in the treatment of postmenopausal patients with estrogen receptor(ER)-positive adjuvant and advanced breast cancer. We aimed to determine the predictive value of a multigene mRNA-based mathematical algorithm (Drug Response Predictor (DRP)) for benefit of exemestane. The DRP is founded on measuring the full cancer transcriptome in sensitive and drug resistant cell lines compared with expression patterns in tumors and broadly validated in several studies (Wang et al. JNCI (2013) 105 (17): 1284-1291.) (Knudsen, S. et al. PLoS One (2014) 9(2): e87415.) (Christensen, TD et al. J Clin Oncol (2016) 34: suppl; abstr e12056.) (Kappel, IB et al. J Clin Oncol (2016) 34: suppl; abstr e20007.). Methods: Among 838 consecutive patients from a DBCG cohort with advanced breast cancer treated at 10 participating sites we identified 163 patients who between November 2008 and November 2015 initiated exemestane. All but one patient were ER-positive. Patients were evaluated every 3 to 4 months using CT scans and clinical examination. After patient informed consent mRNA was extracted and assayed on Affymetrix Gene Chip U133p2 arrays from formalin fixed paraffin embedded diagnostic biopsies. The primary endpoint was progression free survival (PFS). Analysis of the DRP’s ability to predict PFS was performed using a Cox regression model adjusted for treatment line. Results: Median PFS was 8.5 months. Of the 163 patients, 101 received prior adjuvant antihormone therapy and 60 did not. Data regarding adjuvant therapy was inaccessible for two patients. Hazard ratios for patients with predicted good vs. poor effect of exemestane are shown in the table. Conclusions: In a clinical setting, a mathematical algorithm using mRNA from a diagnostic biopsy can in patients unexposed to previous adjuvant endocrine therapy with statistical significance predict who will benefit from exemestane. [Table: see text] |
| Databáze: | OpenAIRE |
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