The EndoPredict score predicts response to neoadjuvant chemotherapy and neoendocrine therapy in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer patients from the ABCSG-34 trial

• Published in: European journal of cancer (1990) 2020-07, Vol.134, p.99-106
• Main Authors: Dubsky, Peter C., Singer, Christian F., Egle, Daniel, Wette, Viktor, Petru, Edgar, Balic, Marija, Pichler, Angelika, Greil, Richard, Petzer, Andreas L., Bago-Horvath, Zsuzsanna, Fesl, Christian, Meek, Stephanie M., Kronenwett, Ralf, Rudas, Margaretha, Gnant, Michael, Filipits, Martin
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biomarkers; Breast cancer; Breast neoplasms; Cancer therapies; Chemotherapy; Drug therapy; Endocrine therapy; Epidermal growth factor; ErbB-2 protein; Estrogen receptors; Estrogens; Growth factors; Health risks; Hormonal; Menopause; Neoadjuvant therapy; Prognosis; Receptors; Risk; Tumors
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2020.04.020

Neoadjuvant 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. Hormone 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). Patients 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]). The 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. •A 12-gene molecular score predicted response to pre-operative neoadjuvant therapy.•Low-score breast tumours were unlikely to respond to neoadjuvant chemotherapy.•Breast tumours with high scores were resistant to neoadjuvant endocrine therapy.