Molecular and cellular composition changes after neoadjuvant letrozole and palbociclib in early luminal breast cancer.
prospective_cohort · Level II
Where this comes from
- Record sourced from PubMed, PMID 41519129.
- Also identified by DOI 10.1016/j.xcrm.2025.102544 and PMC identifier 12866096.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The NeoPAL trial compares neoadjuvant letrozole-palbociclib (LP) with chemotherapy (CT) in 103 patients with high-risk, early luminal breast cancer. At surgery, the NanoString BC360 proliferation score and Ki67 expression are reduced in both arms, together with upregulation of immune-related signatures. Overall, there is very little difference in the changes observed with LP as compared to CT, even in signatures related to response to estrogen and CDK4/6 manipulation. Deconvolution of bulk RNA sequencing (RNA-seq) data reveals high content at baseline in cancer cells, immunosuppressive cancer-associated fibroblasts, FOXP3+ CD4<sup>+</sup> regulatory T lymphocytes, and TREM2+ macrophages. In contrast, myoepithelial cells, normal-like fibroblasts, FOLR2+ macrophages, and SELL+ CD4<sup>+</sup> T lymphocytes accumulate after treatment in both arms. A low ROR score is observed at surgery in 63.3% and 43.5% of patients in the LP and CT arms, respectively. No 3-year breast cancer-specific survival events are observed in these patients. These data provide a rationale for CT-sparing trials in this setting.
Medical subject headings
- Letrozole
- Breast Neoplasms
- Pyridines
- Piperazines
- Antineoplastic Combined Chemotherapy Protocols