ArticleOncotarget2016
A gene expression signature of retinoblastoma loss-of-function is a predictive biomarker of resistance to palbociclib in breast cancer cell lines and is prognostic in patients with ER positive early breast cancer.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03644186 (Phase II Open-label, Multicentre, Randomized Trial of Neoadjuvant Palbociclib in Combination With Hormonal Therapy and HER2 Blockade Versus Paclitaxel in Combination With HER2 Blockade for Postmenopausal Patients With Hormone Receptor Positive/HER2 Positive Early Breast Cancer), which is not on this map. Cited by 96 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase II Open-label, Multicentre, Randomized Trial of Neoadjuvant Palbociclib in Combination With Hormonal Therapy and HER2 Blockade Versus Paclitaxel in Combination With HER2 Blockade for Postmenopausal Patients With Hormone Receptor Positive/HER2 Positive Early Breast Cancer
Who cites it
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 162 citations in OpenAlex.
- Clinical Utility of CDK4/6 Inhibitors in Sarcoma: Successes and Future Challenges.JCO precision oncology · 2022Pooled it
- Neoadjuvant palbociclib and endocrine therapy versus chemotherapy in ER + /HER2- breast cancer: a randomized phase II trial.Nature communications · 2026Trial
- A Phase II Study of Abemaciclib for Patients with Retinoblastoma-Positive, Metastatic Triple-Negative Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Immune Checkpoint Blockade Outcome in Small-Cell Lung Cancer and Its Relationship With Retinoblastoma Mutation Status and Function.JCO precision oncology · 2022Trial
- Potent Cell-Cycle Inhibition and Upregulation of Immune Response with Abemaciclib and Anastrozole in neoMONARCH, Phase II Neoadjuvant Study in HRClinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- Impact of aromatase inhibitor treatment on global gene expression and its association with antiproliferative response in ER+ breast cancer in postmenopausal patients.Breast cancer research : BCR · 2019Trial
- Molecular signatures of triple-negative breast cancer cells acquiring palbociclib resistance via continuous exposure.Oncology letters · 2026Article
- Article
- CDKN1B inactivation impacts ER signaling and drives resistance to endocrine therapy in breast cancer.British journal of cancer · 2026Article
- Review
- Synthetic lethality between RB-loss and E2F3 inhibition in small cell cancers targeted by pyrimidine synthesis blockade.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Rb expression in metastatic ER-positive breast cancer: implications for precision oncology.Breast cancer research and treatment · 2026Article
- Mammary small cell neuroendocrine carcinomas that showed excellent pathologic response following etoposide-based neoadjuvant chemotherapy.Breast cancer research and treatment · 2025Article
- Gene expression-based rationale for investigating CDK4/6 inhibitors in primitive myelofibrosis.Leukemia · 2025Article
- Single-cell transcriptomics reveals biomarker heterogeneity linked to CDK4/6 Inhibitor resistance in breast cancer cell lines.NPJ breast cancer · 2025Article
- Article
- Proteogenomic discovery ofScience advances · 2025Article
- Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i): Mechanisms of resistance and where to find them.Breast (Edinburgh, Scotland) · 2025Review
- Optimizing therapeutic approaches for HR+/HER2- advanced breast cancer: clinical perspectives on biomarkers and treatment strategies post-CDK4/6 inhibitor progression.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- CDK4/6 Inhibitor Resistance in ER+ Breast Cancer.Advances in experimental medicine and biology · 2025Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Palbociclib is a CDK4/6 inhibitor that received FDA approval for treatment of hormone receptor positive (HR+) HER2 negative (HER2neg) advanced breast cancer. To better personalize patients treatment it is critical to identify subgroups that would mostly benefit from it. We hypothesize that complex alterations of the Retinoblastoma (Rb) pathway might be implicated in resistance to CDK4/6 inhibitors and aim to investigate whether signatures of Rb loss-of-function would identify breast cancer cell lines resistant to palbociclib. We established a gene expression signature of Rb loss-of-function (RBsig) by identifying genes correlated with E2F1 and E2F2 expression in breast cancers within The Cancer Genome Atlas. We assessed the RBsig prognostic role in the METABRIC and in a comprehensive breast cancer meta-dataset. Finally, we analyzed whether RBsig would discriminate palbociclib-sensitive and -resistant breast cancer cells in a large RNA sequencing-based dataset. The RBsig was associated with RB1 genetic status in all tumors (p <7e-32) and in luminal or basal subtypes (p < 7e-11 and p < 0.002, respectively). The RBsig was prognostic in the METABRIC dataset (discovery: HR = 1.93 [1.5-2.4] p = 1.4e-08; validation: HR = 2.01 [1.6-2.5] p = 1.3e-09). Untreated and endocrine treated patients with estrogen receptor positive breast cancer expressing high RBsig had significantly worse recurrence free survival compared to those with low RBsig (HR = 2.37 [1.8 - 3.2] p = 1.87e-08 and HR = 2.62 [1.9- 3.5] p = 8.6e-11, respectively). The RBsig was able to identify palbociclib resistant and sensitive breast cancer cells (ROC AUC = 0,7778). Signatures of RB loss might be helpful in personalizing treatment of patients with HR+/HER2neg breast cancer. Further validation in patients receiving palbociclib is warranted.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.