Molecular and cellular composition changes after neoadjuvant letrozole and palbociclib in early luminal breast cancer
Year: 2026
Type: article
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 + regulatory T lymphocytes, and TREM2+ macrophages. In contrast, myoepithelial cells, normal-like fibroblasts, FOLR2+ macrophages, and SELL+ CD4 + 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.
Source: Cell Reports Medicine
Authors: Paul Cottu, Yann Kieffer, Jerome Lemonnier, Véronique D’hondt, Francois P. Duhoux, Céline Callens, David Gentien, Cécile Reyes, Anais Boulai, Isabelle Desmoulins, Marie-Ange Mouret-Reynier, Christelle Levy, Pierre-Etienne Heudel, Florence Dalenc, Julien Grenier, Laetitia Fuhrmann, Sylvain Baulande, Suzette Delaloge, Fatima Mechta-Grigoriou, Anne Vincent-Salomon
Institutions: Université Paris Cité, Institut Curie, Inserm, Université Paris Sciences et Lettres, La Ligue Contre le Cancer, UniCancer Group, Cliniques Universitaires Saint-Luc, UCLouvain, Centre Georges François Leclerc, Centre Jean Perrin, Centre François Baclesse, Centre Léon Bérard, Institut universitaire du cancer de Toulouse Oncopole, Institut Sainte Catherine, Institut Gustave Roussy
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: Pfizer, Pfizer France
Award: G3848155363
OpenAlex ID: W7119895638