Skip to content
DraconiticResearch
Search Sources API
197,768 studies31 sourcesUpdated 6 min ago
Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Genetic Variation in NR1I2 and Palbociclib Safety and Prognosis in Advanced Breast Cancer: An Exploratory Multicenter Study

  • Cristina Arqueros1,2,3,4
  • Marta Andrés1,2,3,4
  • Sònia Servitja2,5,6,7
  • Júlia Giner8
  • Ariadna Tibau1,4,9
  • Maria Borrell10,11
  • Sergio Martinez-Recio1,4
  • Agustí Barnadas1,4
  • Juliana Salazar4
11 affiliations
  1. 1Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
  2. 2Spanish Group for Breast Cancer Research (GEICAM), 08041 Barcelona, Spain
  3. 3Department of Medicine, Faculty of Medicine, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain
  4. 4Translational Medical Oncology Laboratory, Institut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, Spain
  5. 5Medical Oncology, Hospital del Mar, 08003 Barcelona, Spain
  6. 6Hospital del Mar Research Institute, 08003 Barcelona, Spain
  7. 7Department of Medicine and Life Science, Universitat Pompeu Fabra, 08003 Barcelona, Spain
  8. 8Medical Oncology Department, Corporació Sanitària Parc Taulí, 08208 Sabadell, Spain
  9. 9Program on Regulation, Therapeutics and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02120, USA
  10. 10Medical Oncology Department, Vall d’Hebron Hospital, 08035 Barcelona, Spain
  11. 11Breast Cancer Group, Vall d’Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain
Open at sourceDOICite

Abstract

Palbociclib has shown survival benefits in hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer. At present, however, no genetic predictors of palbociclib-related hematological toxicity have been validated for clinical use. The aim of this study was to evaluate whether genetic variants are associated with palbociclib toxicity and patient prognosis. Multicenter study of 113 patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer treated with palbociclib plus endocrine therapy. Genotyping of DNA from blood samples was performed to determine 18 variants in seven target genes (CYP3A4, SULT2A1, ABCB1, ABCG2, NR1I2, POR, and CDKN1B). Association analyses were performed to assess the relationship between the genetic variants and treatment-related toxicity and survival outcomes. Sixty-seven patients (59.3%) developed grade 3/4 neutropenia, 62 (54.9%) experienced disease progression, and 43 (38.1%) died. Although none of the univariate associations remained significant after Bonferroni correction, the multivariate analysis, adjusted for clinical variables, revealed several nominally significant associations. The NR1I2 gene variants rs6785049 (p = 0.01) and rs3732360 (p = 0.009) were associated with grade 3/4 neutropenia. The NR1I2 rs6785049 variant was associated with palbociclib treatment interruption (p = 0.03) and with worse progression-free (p = 0.003) and overall survival (p = 0.02). The findings of this exploratory study suggest potential associations between the NR1I2 rs6785049 variant and treatment toxicity and survival outcomes in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer treated with palbociclib. However, these hypothesis-generating findings need to be independently validated.

Related

  1. Circulating and tumor microenvironment immunomarkers associate with immunotherapy efficacy in advanced bladder urothelial carcinoma: an exploratory multicenter study integrating genomic and immunophenotypic profiling
    Sha Liu, Junjun Lu, Zhaojie Lyu +7
    ImmunotherapyPeer-reviewedLicence not statedFull textOncologyPMC
  2. Cost-effectiveness of inavolisib plus palbociclib/fulvestrant versus palbociclib/fulvestrant for PIK3CA-mutated advanced breast cancer in China
    Zuojuan Xiang, Xiaojuan Chen, Ling Ma
    Frontiers in PharmacologyPeer-reviewedCC BY 4.0Full textPharmacology & toxicologyCrossrefDOAJ
  3. The LIP score: a pathophysiology-driven tool for sepsis screening and prognosis—a multicenter prospective study
    Bin Liu, Fan Zhang, Yuan Yan +19
    BMC MedicinePeer-reviewedCC BY-NC-ND 4.0Epidemiology & public healthCrossref
  4. An Early Longitudinal Decrease in Platelet Count Is Associated With Poor Prognosis in Acute Myocardial Infarction Patients: A Multicenter Retrospective Study.
    Tianlai Lin, Jingqing Xu, Xiaoling Zeng +4
    Clinical cardiologyPeer-reviewedCC BYFull textCardiovascular medicineEurope PMC
  5. Multimodal prediction of neoadjuvant chemotherapy response in locally advanced gastric cancer: a multicenter cohort study
    Ping’an Ding, Honghai Guo, Jiaxuan Yang +12
    BMC MedicinePeer-reviewedCC BY 4.0General medicineCrossref

Cite

BibTeXRIS
BibTeX
@article{arqueros2026genetic,
  title = {{Genetic Variation in NR1I2 and Palbociclib Safety and Prognosis in Advanced Breast Cancer: An Exploratory Multicenter Study}},
  author = {Cristina Arqueros and Marta Andrés and Sònia Servitja and Júlia Giner and Ariadna Tibau and Maria Borrell and Sergio Martinez-Recio and Agustí Barnadas and Juliana Salazar},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = sep,
  doi = {10.3390/ijms27188310},
  url = {https://www.mdpi.com/1422-0067/27/18/8310},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Genetic Variation in NR1I2 and Palbociclib Safety and Prognosis in Advanced Breast Cancer: An Exploratory Multicenter Study
AU  - Cristina Arqueros
AU  - Marta Andrés
AU  - Sònia Servitja
AU  - Júlia Giner
AU  - Ariadna Tibau
AU  - Maria Borrell
AU  - Sergio Martinez-Recio
AU  - Agustí Barnadas
AU  - Juliana Salazar
PY  - 2026
DA  - 2026/09/18
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27188310
UR  - https://www.mdpi.com/1422-0067/27/18/8310
AB  - Palbociclib has shown survival benefits in hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer. At present, however, no genetic predictors of palbociclib-related hematological toxicity have been validated for clinical use. The aim of this study was to evaluate whether genetic variants are associated with palbociclib toxicity and patient prognosis. Multicenter study of 113 patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer treated with palbociclib plus endocrine therapy. Genotyping of DNA from blood samples was performed to determine 18 variants in seven target genes (CYP3A4, SULT2A1, ABCB1, ABCG2, NR1I2, POR, and CDKN1B). Association analyses were performed to assess the relationship between the genetic variants and treatment-related toxicity and survival outcomes. Sixty-seven patients (59.3%) developed grade 3/4 neutropenia, 62 (54.9%) experienced disease progression, and 43 (38.1%) died. Although none of the univariate associations remained significant after Bonferroni correction, the multivariate analysis, adjusted for clinical variables, revealed several nominally significant associations. The NR1I2 gene variants rs6785049 (p = 0.01) and rs3732360 (p = 0.009) were associated with grade 3/4 neutropenia. The NR1I2 rs6785049 variant was associated with palbociclib treatment interruption (p = 0.03) and with worse progression-free (p = 0.003) and overall survival (p = 0.02). The findings of this exploratory study suggest potential associations between the NR1I2 rs6785049 variant and treatment toxicity and survival outcomes in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer treated with palbociclib. However, these hypothesis-generating findings need to be independently validated.
SN  - 1422-0067
ER  -