Edlund, Karolina, Madjar, Katrin, Lebrecht, Antje, Aktas, Bahriye ORCID: 0000-0002-5474-051X, Pilch, Henryk, Hoffmann, Gerald, Hofmann, Manfred, Kolberg, Hans-Christian, Boehm, Daniel, Battista, Marco, Seehase, Martina, Stewen, Kathrin, Gebhard, Susanne, Cadenas, Cristina, Marchan, Rosemarie, Brenner, Walburgis, Hasenburg, Annette, Koelbl, Heinz, Solbach, Christine, Gehrmann, Mathias, Tanner, Berno, Weber, Karsten E., Loibl, Sibylle, Sachinidis, Agapios, Rahnenfuehrer, Joerg, Schmidt, Marcus ORCID: 0000-0003-1365-2414 and Hengstler, Jan G. (2021). Gene Expression-Based Prediction of Neoadjuvant Chemotherapy Response in Early Breast Cancer: Results of the Prospective Multicenter EXPRESSION Trial. Clin. Cancer Res., 27 (8). S. 2148 - 2159. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1557-3265

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Abstract

Purpose: Expression-based classifiers to predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) are not routinely used in the clinic. We aimed to build and validate a classifier for pCR after NACT. Patients and Methods: We performed a prospective multicenter study (EXPRESSION) including 114 patients treated with anthracycline/taxane-based NACT. Pretreatment core needle biopsies from 91 patients were used for gene expression analysis and classifier construction, followed by validation in five external cohorts (n = 619). Results: A 20-gene classifier established in the EXPRESSION cohort using a Youden index-based cut-off point predicted pCR in the validation cohorts with an accuracy, AUC, negative predictive value (NPV), positive predictive value, sensitivity, and specificity of 0.811, 0.768, 0.829, 0.587, 0.216, and 0.962, respectively. Alternatively, aiming for a high NPV by defining the cut-off point for classification based on the complete responder with the lowest predicted probability of pCR in the EXPRESSION cohort led to an NPV of 0.960 upon external validation. With this extreme-low cut-off point, a recommendation to not treat with anthracycline/taxane-based NACT would be possible for 121 of 619 unselected patients (19.5%) and 112 of 322 patients with luminal breast cancer (34.8%). The analysis of the molecular subtypes showed that the identification of patients who do not achieve a pCR by the 20-gene classifier was particularly relevant in luminal breast cancer. Conclusions: The novel 20-gene classifier reliably identifies patients who do not achieve a pCR in about one third of luminal breast cancers in both the EXPRESSION and combined validation cohorts.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Edlund, KarolinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Madjar, KatrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lebrecht, AntjeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aktas, BahriyeUNSPECIFIEDorcid.org/0000-0002-5474-051XUNSPECIFIED
Pilch, HenrykUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoffmann, GeraldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofmann, ManfredUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kolberg, Hans-ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boehm, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Battista, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seehase, MartinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stewen, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gebhard, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cadenas, CristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marchan, RosemarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brenner, WalburgisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hasenburg, AnnetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koelbl, HeinzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Solbach, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gehrmann, MathiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tanner, BernoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, Karsten E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loibl, SibylleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sachinidis, AgapiosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rahnenfuehrer, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, MarcusUNSPECIFIEDorcid.org/0000-0003-1365-2414UNSPECIFIED
Hengstler, Jan G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-601925
DOI: 10.1158/1078-0432.CCR-20-2662
Journal or Publication Title: Clin. Cancer Res.
Volume: 27
Number: 8
Page Range: S. 2148 - 2159
Date: 2021
Publisher: AMER ASSOC CANCER RESEARCH
Place of Publication: PHILADELPHIA
ISSN: 1557-3265
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PATHOLOGICAL COMPLETE RESPONSE; CYCLOPHOSPHAMIDE CHEMOTHERAPY; NAB-PACLITAXEL; FLUOROURACIL; DOXORUBICIN; SIGNATURE; DOCETAXEL; FAMILY; WOMEN; CONSTRUCTIONMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60192

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