2026-04-29T07:25:12Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/197492024-11-29T20:23:35Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Mouron, Silvana author Bueno, Maria J author Muñoz, Manuel author Torres, Raul author Rodríguez, Sandra author Apala, Juan V author Silva, Jorge author Sánchez-Bayona, Rodrigo author Manso, Luis author Guerra, Juan author Rodriguez-Lajusticia, Laura author Malon, Diego author Malumbres Martinez, Marcos author Quintela Fandino, Miguel Angel author 2023-03-01 CDK4/6 inhibitors benefit a minority of patients who receive them in the breast cancer adjuvant setting. p27Kip1 is a protein that inhibits CDK/Cyclin complexes. We hypothesized that single-nucleotide polymorphisms that impaired p27Kip1 function could render patients refractory to endocrine therapy but responsive to CDK4/6 inhibitors, narrowing the patient subpopulation that requires CDK4/6 inhibitors. We found that the p27Kip1 V109G single-nucleotide polymorphism is homozygous in approximately 15% of hormone-positive breast cancer patients. Polymorphic patients experience rapid failure in response to endocrine monotherapy compared with wild-type or heterozygous patients in the first-line metastatic setting (progression-free survival: 92 vs 485 days, P < .001); when CDK4/6 inhibitors are added, the differences disappear (progression-free survival: 658 vs 761 days, P = .92). As opposed to wild-type p27Kip1, p27Kip1 V109G is unable to suppress the kinase activity of CDK4 in the presence of endocrine inhibitors; however, palbociclib blocks CDK4 kinase activity regardless of the p27Kip1 status. p27Kip1 genotyping could constitute a tool for treatment selection. JNCI Cancer Spectr . 2023;7(2):pkad014. http://hdl.handle.net/20.500.12105/19749 36806942 10.1093/jncics/pkad014 2515-5091 JNCI cancer spectrum p27Kip1 V109G as a biomarker for CDK4/6 inhibitors indication in hormone receptor-positive breast cancer.