Molecular and cellular composition changes after neoadjuvant letrozole and palbociclib in early luminal breast cancer
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.
Authors
- Véronique D’Hondt (ORCID: https://orcid.org/0000-0001-5238-4032)
- David Gentien (ORCID: https://orcid.org/0000-0001-8317-5188)
- Isabelle Desmoulins (ORCID: https://orcid.org/0000-0002-1251-5648)
- Florence Dalenc (ORCID: https://orcid.org/0000-0002-9854-4182)
- Laetitia Fuhrmann (ORCID: https://orcid.org/0000-0003-1755-6307)
- Sylvain Baulande (ORCID: https://orcid.org/0000-0003-3104-1684)
- Céline Callens
- Pierre-Étienne Heudel (ORCID: https://orcid.org/0000-0002-2155-549X)
- Anaïs Boulai
- Cécile Réyès (ORCID: https://orcid.org/0009-0001-2281-0827)
- Yann Kieffer
- Suzette Delaloge
- Jerome Lemonnier
- Julien Grenier
- Anne Vincent-Salomon
- Fatima Mechta-Grigoriou
- Francois P. Duhoux
- Christelle Levy
- Marie-Ange Mouret-Reynier
- Paul Cottu
Institutions
- Cliniques Universitaires Saint-Luc (BE)
- Inserm (FR)
- Université Paris Cité (FR)
- Université Paris Sciences et Lettres (FR)
- Institut Gustave Roussy (FR)
- Centre Georges François Leclerc (FR)
- La Ligue Contre le Cancer (FR)
- Intergroupe Francophone de Cancérologie Thoracique (FR)
- Centre François Baclesse (LU)
- Centre Léon Bérard (FR)
- Centre Jean Perrin (FR)
- Centre de Recherche en Cancérologie de Lyon (FR)
- Institut Claudius Regaud (FR)
- Institut de Recherche en Cancérologie de Montpellier (FR)
- UniCancer Group (FR)
- Institut Sainte Catherine (FR)
- Institut Curie (FR)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2026-01-01
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102544
- Primary Topic
- Advanced Breast Cancer Therapies
- Type
- article
- Field-Weighted Citation Impact
- 0.00