Pernas, SòniaSanfeliu, EstherVillacampa, GuillermoSalvador, JavierPerelló, AntoniaGonzález, XavierJiménez, BegoñaMerino, MaríaPalacios, PatriciaPascual, TomásAlba, EmilioVillanueva, LoreaChillara, SamyuktaFerrero Cafiero, Juan ManuelGalvan, PatriciaPrat Aparicio, AleixCiruelos, Eva2025-03-042025-03-042024-11-262374-4677https://hdl.handle.net/2445/219439With the incorporation of cyclin-dependent kinase inhibitors in early breast cancer (BC), a better identification of biomarkers is needed. The PROMETEO II trial aimed to evaluate the antitumor activity of palbociclib plus letrozole and to identify response biomarkers in patients with operable HR+/HER2- BC and residual disease after neoadjuvant chemotherapy (NAC). The primary endpoint was the rate of complete cell cycle arrest (CCCA), centrally determined by Ki67 <= 2.7% at surgery. A comprehensive translational analysis was conducted. At surgery, the CCCA rate was 59.1%, with a 44.2% decrease in Ki67 from the end of NAC. Changes in intrinsic subtypes occurred in 48% of patients, with proliferation genes suppressed, and immune genes more upregulated in tumors with CCCA. Overall, 14% of tumors were classified as PD-L1+ after palbociclib. Nine patients experienced grade 3 adverse events (AEs). Palbociclib showed an anti-proliferative effect, with increased immune infiltration in residual tumors with CCCA.Trial registration: Palbociclib Plus Letrozole in Hormone Receptor Positive Residual Disease After Neoadjuvant Chemotherapy (PROMETEO II) ClinicalTrial.gov number NCT04130152. Study registration; October 17, 2019.8 p.application/pdfengcc-by-nc-nd (c) Pernas, Sonia et al., 2024http://creativecommons.org/licenses/by-nc-nd/3.0/es/Càncer de mamaQuimioteràpia del càncerBreast cancerCancer chemotherapyinfo:eu-repo/semantics/article2024-12-10info:eu-repo/semantics/openAccess39592624