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

Abstract

Background: 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 â ) to predict response to NaCT or NET within the ABCSG-34 trial. Patients and methods: 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). Results: 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 NaCTtreated and high-risk NET-treated tumours responded poorly (NPV 100% [95% CI 66.4% e100%] and NPV 92.3% [95% CI 79.1%e98.4%], respectively]. The 12-gene MS significantly predicted treatment response for NaCT (AUC 0.736 [95% CI 0.63e0.84]) and NET (AUC 0.726 [95% CI 0.60e0.85]). Conclusions: 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.

Predicting the response of neoadjuvant chemotherapy in hormone receptor- positive and HER2-negative breast cancer with axillary lymph node metastasis by a multigene assay (GenesWell™ BCT)

“…Although this study is a retrospective, single-center study with a small sample size, it is signi cant as it predicted the NACT response from the core biopsy sample for the rst time using the BCT score. In addition, efforts have also been made to predict the responsiveness of neoadjuvant endocrine therapy (NET) by multigene assay 21,26 . Further studies are needed to prove the predictive potential of the BCT score response to NET in Asian patients with BC because many multigene assays have been developed with a focus on the Western population 27,28 .…”

Neoadjuvant Endocrine Therapy in Breast Cancer Management: State of the Art

“…Akashi-Tanaka et al, in a small cohort of 43 patients, also suggested that a low RS predicted better RFS than for patients with intermediate or high RS (5-year RFS, 100% vs. 84% and 73%, respectively) [70]. Using Endopredict in 83 patients treated with NET, a low-risk 12-gene molecular score (MS) was also associated with a higher RCB 0-1 rate (27%) than a high-risk MS score (8%) [47].…”

“…Given the fairly recent use of this score, only limited data are available concerning RCB after NET. In the ABCSG-34 trial, NET-treated patients (n = 83) were less likely to achieve RCB 0-1 (18.1%) compared to NCT-treated patients (24.6%) [47]. The RCB score was used in the NeoPAL and CORALLEEN trials, which both randomized patients to receive either NET combined with a CDK4/6 inhibitor or NCT.…”

The Present and Future of Neoadjuvant Endocrine Therapy for Breast Cancer Treatment

“…Genomic assays have become a very useful tool for guiding adjuvant treatments in early ER+ breast cancer. The possibility of performing these assays in the core biopsy increases their utility to the neoadjuvant setting, and most of them have already demonstrated their capacity for predicting NCT response [ 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 ]. We will now review those that have been investigated in the context of NET.…”

“…However, in the neoadjuvant setting, only the molecular analysis (EP) is possible. Dubsky et al analyzed 217 samples of diagnostic core biopsies from the ABCSG-34 trial [ 106 ], in which women had already been selected to receive NCT or NET according to clinical or immunohistochemical criteria. Tumors with a low molecular score (MS) were unlikely to benefit from NCT (NPV 100% (95% CI, 66.4%–100%)), whereas a high MS predicted resistance to NET (NPV 92.3% (95% CI, 79.1%–98.4%)).…”