• Peter C Dubsky, Christian F Singer, Daniel Egle, Viktor Wette, Edgar Petru, Marija Balic, Angelika Pichler, Richard Greil, Andreas L Petzer, Zsuzsanna Bago-Horvath, Christian Fesl, Stephanie M Meek, Ralf Kronenwett, Margaretha Rudas, Michael Gnant, Martin Filipits, and Austrian Breast and Colorectal Cancer Study Group.
• Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Breast Center St. Anna, Lucerne, Switzerland. Electronic address: peter.dubsky@hirslanden.ch.
• Eur. J. Cancer. 2020 Jul 1; 134: 99-106.

BackgroundNeoadjuvant chemotherapy (NaCT) and neoadjuvant endocrine therapy (NET) can reduce pre-operative tumour burden in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer. This prospective translational study assessed the ability of a 12-gene molecular score (MS; EndoPredict®) to predict response to NaCT or NET within the ABCSG-34 trial.Patients And MethodsHormone receptor (HR)-positive, HER2-negative samples from patients in the ABCSG-34 randomized phase II trial were selected and EndoPredict testing was performed to generate a 12-gene MS. ABCSG-34 patients were assigned to receive either NaCT or NET based on menopausal status, HR expression, grade and Ki67. Response was measured by residual cancer burden (RCB).ResultsPatients selected for NaCT generally had high-risk disease by 12-gene MS (125/134), while slightly more patients treated with NET had low-risk disease (44/83). Low-risk NaCT-treated and high-risk NET-treated tumours responded poorly (NPV 100% [95% CI 66.4%-100%] and NPV 92.3% [95% CI 79.1%-98.4%], respectively]. The 12-gene MS significantly predicted treatment response for NaCT (AUC 0.736 [95% CI 0.63-0.84]) and NET (AUC 0.726 [95% CI 0.60-0.85]).ConclusionsThe 12-gene MS predicted RCB after treatment with neoadjuvant therapies for patients with HR-positive, HER2-negative early-stage breast cancer. Tumours with low MS were unlikely to benefit from NaCT, whereas a high MS predicted resistance to NET. This additional biologic information can aid personalized treatment selection in daily practice and builds a strong rationale to use EndoPredict in biomarker-driven studies in the neoadjuvant setting.Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

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