Supplementary Data from Gene Expression–Based Prediction of Neoadjuvant Chemotherapy Response in Early Breast Cancer: Results of the Prospective Multicenter EXPRESSION Trial

Edlund, Karolina; Madjar, Katrin; Lebrecht, Antje; Aktas, Bahriye; 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; Rahnenführer, Jörg; Schmidt, Marcus; Hengstler, Jan G.

doi:10.1158/1078-0432.22483439.v1

Supplementary Data from Gene Expression–Based Prediction of Neoadjuvant Chemotherapy Response in Early Breast Cancer: Results of the Prospective Multicenter EXPRESSION Trial

journal contribution

posted on 2023-03-31, 23:10 authored by Karolina Edlund, Katrin Madjar, Antje Lebrecht, Bahriye Aktas, Henryk Pilch, Gerald Hoffmann, Manfred Hofmann, Hans-Christian Kolberg, Daniel Boehm, Marco Battista, Martina Seehase, Kathrin Stewen, Susanne Gebhard, Cristina Cadenas, Rosemarie Marchan, Walburgis Brenner, Annette Hasenburg, Heinz Koelbl, Christine Solbach, Mathias Gehrmann, Berno Tanner, Karsten E. Weber, Sibylle Loibl, Agapios Sachinidis, Jörg Rahnenführer, Marcus Schmidt, Jan G. Hengstler

Pipeline for classifier construction (a), PCA of the EXPRESSION cohort (b), performance of classifier variants (c), cross-tables of complete responders and non-complete responders (d), classifier performance (e) and calibration (f), comparison with published classifiers (g), and the AUC for of classifiers from ranked probesets (h)

Funding

Federal Ministry of Education and Research

History

ARTICLE ABSTRACT

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. 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). 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. 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.