ER positive + HER-2 negative

Three drugs of the class, abemaciclib, palbociclib and ribociclib, are currently approved in partially overlapping indications. A prominent downstream target of E2F that is repeatedly discussed in several studies is cyclin E. Key resistance mechanisms interfering with CDK4/6 inhibitor efficacy have been identified but are not yet used clinically. Diverse resistance mechanisms observed in individual cases would require individualized approaches to re-sensitize cancer cells and patients to cell cycle inhibition.

P1/2, N=99, Recruiting, Forward Pharmaceuticals Co., Ltd. | Phase classification: P1 --> P1/2 | Trial completion date: Feb 2026 --> Mar 2028 | Trial primary completion date: Nov 2025 --> Mar 2026

P1/2, N=24, Not yet recruiting, University of Chicago

S.J.L. received funding from an NHMRC Project Grant ID: 1125433.

P=N/A, N=70, Not yet recruiting, Assiut University

This IHC-based model predicts pCR and helps identify subgroups in which pCR is associated with meaningful survival benefit following NAC in ER-positive/HER2-negative breast cancers. High-scoring patients may benefit from NAC, while patients with low- or intermediate-scores may be better managed with surgery and endocrine therapy. This model may support personalized treatment decisions regarding NAC.

LRG1 significantly predicted three-year overall survival in patients with metastatic breast cancer, supporting its potential as a prognostic biomarker.

Additionally, a 33-gene signature that predicted neoadjuvant Ki67 response to ANA/PAL was prognostic in a metastatic validation cohort. These findings underscore dysregulated oncogenic pathways as potential resistance mechanisms and biomarkers of response to CDK4/6i.

At the time of tracheotomy, biopsy evaluation revealed that the metastatic left supraclavicular lymph nodes were ER- and HER2-positive; therefore, the treatment was switched to a trastuzumab, pertuzumab, and docetaxel(TPD)combination for HER2-positive recurrent breast cancer. However, PET-CT revealed increased accumulation in the recurrent lesions, and the treatment was switched to trastuzumab deruxtecan (T-DXd). The accumulation of recurrent foci became less pronounced and the patient continued to progress without further deterioration.

In summary, we present the most comprehensive matched multiomic dataset from ER-positive/HER2-negative BC tumors, not only serving as an invaluable resource for further advancing precision medicine but also allowing the discovery of potential biomarkers and providing unique insights into metastatic processes.

While prospective studies with modern treatment regimens are needed to establish clinical utility, Chemo-prAIdict Breast is a new tool for identifying eBC that are differentially sensitive to standard NAC, and could help to select the most appropriate treatment strategy in HER2 + , ER+ /HER2- and TN eBC.