Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2022
Modulation of the Estrogen/erbB2 Receptors Cross-talk by CDK4/6 Inhibition Triggers Sustained Senescence in Estrogen Receptor- and ErbB2-positive Breast Cancer.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02530424 ("Neo-Adjuvant Treatment With the CDK4,6 Inhibitor Palbociclib in HER2-positive and ER-positive Breast Cancer), which is not on this map. Cited by 22 papers.
What it found
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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.
"Neo-Adjuvant Treatment With the CDK4,6 Inhibitor Palbociclib in HER2-positive and ER-positive Breast Cancer: Effect on Ki67 and Apoptosis Before, During and After Treatment "
Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Role of ctDNA in Predicting the Outcome of Patients with Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer Treated with First-line Ribociclib and Letrozole: BioItaLEE Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Determinants of response and molecular dynamics in HER2+ER+ breast cancers from the NA-PHER2 trial receiving HER2-targeted and endocrine therapies.Nature communications · 2025Trial
- Clinical characterization, prognostic, and predictive values of HER2-low in patients with early breast cancer in the PALLAS trial (ABCSG-42/AFT-05/BIG-14-13/PrE0109).Breast cancer research : BCR · 2024Trial
- Dynamic Evolution of HER2 Expression Following Neoadjuvant Therapy and Its Association With Treatment Response and Prognosis in Breast Cancer: A Large-Scale Retrospective Study.World journal of surgery · 2026Article
- Risk Factors Influencing Efficacy and Prognosis Evaluation of Neoadjuvant Systemic Therapy in Triple-Positive Breast Cancer.The Kaohsiung journal of medical sciences · 2026Article
- Deruxtecan-based antibody-drug-conjugates induce senescence in HER2-positive breast cancer.Scientific reports · 2026Article
- Stigmasterol reverses rituximab resistance in diffuse large B-cell lymphoma via the MAPK1 signaling pathway.Translational cancer research · 2026Article
- Spatial molecular analyses reveal key features associated with response to KN026 in advanced HER2-positive breast cancer.British journal of cancer · 2026Article
- Emerging Targeted and Multimodal Therapeutic Strategies in Breast Cancer: A Comprehensive Review.Breast cancer (Dove Medical Press) · 2026Review
- The role of dual-tracer PET imaging with ER and HER2 in patients with metastatic breast cancer: a pilot study.Annals of nuclear medicine · 2025Article
- Efficacy and Predictability of Cyclin-Dependent Kinase 4/6 Inhibitors in HER2-Positive Breast Cancer.Cancers · 2025Review
- CDK4/6 inhibitor PD-0332991 suppresses hepatocarcinogenesis by inducing senescence of hepatic tumor-initiating cells.Journal of advanced research · 2025Article
- Review
- Correlation Between PIK3R1 Expression and Cell Growth in Human Breast Cancer Cell Line BT-474 and Clinical Outcomes.World journal of oncology · 2025Article
- Hormone Receptor-Positive/HER2-Positive Breast Cancer: Hormone Therapy and Anti-HER2 Treatment: An Update on Treatment Strategies.Journal of clinical medicine · 2024Review
- Developing liver-targeted naringenin nanoparticles for breast cancer endocrine therapy by promoting estrogen metabolism.Journal of nanobiotechnology · 2024Article
- Genomic Alterations of Tumors in HER2-Low Breast Cancers.International journal of molecular sciences · 2024Article
- Modulation of tumor plasticity by senescent cells: Deciphering basic mechanisms and survival pathways to unravel therapeutic options.Genetics and molecular biology · 2024Article
- Reversal of tamoxifen resistance by artemisinin in ER+ breast cancer: bioinformatics analysis and experimental validation.Oncology research · 2024Article
- Cellular senescence in the response of HRJournal of translational medicine · 2023Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe interplay between estrogen receptor (ER) and erbB tyrosine-kinase receptors (RTK) impacts growth and progression of ER-positive (ER+)/HER2-positive (HER2+) breast cancer and generates mitogenic signals converging onto the Cyclin-D1/CDK4/6 complex. We probed this cross-talk combining endocrine-therapy (fulvestrant), dual HER2-blockade (trastuzumab and pertuzumab), and CDK4/6-inhibition (palbociclib; PFHPert). EXPERIMENTAL
designCytotoxic drug effects, interactions, and pharmacodynamics were studied after 72 hours of treatment and over 6 more days of culture after drug wash-out in three ER+/HER2+, two HER2low, and two ER-negative (ER-)/HER2+ breast cancer cell lines. We assessed gene-expression dynamic and association with Ki67 downregulation in 28 patients with ER+/HER2+ breast cancer treated with neoadjuvant PFHPert in NA-PHER2 trial (NCT02530424).
resultsIn vitro, palbociclib and/or fulvestrant induced a functional activation of RTKs signalling. PFHPert had additive or synergistic antiproliferative activity, interfered with resistance mechanisms linked to the RTKs/Akt/MTORC1 axis and induced sustained senescence. Unexpected synergism was found in HER2low cells. In patients, Ki67 downregulation at week 2 and surgery were significantly associated to upregulation of senescence-related genes (P = 7.7E-4 and P = 1.8E-4, respectively). Activation of MTORC1 pathway was associated with high Ki67 at surgery (P = 0.019).
conclusionsResistance associated with the combination of drugs targeting ER and HER2 can be bypassed by cotargeting Rb, enhancing transition from quiescence to sustained senescence. MTORC1 pathway activation is a potential mechanism of escape and RTKs functional activation may be an alternative pathway for survival also in ER+/HER2low tumor. PFHPert combination is an effective chemotherapy-free regimen for ER+/HER2+ breast cancer, and the mechanistic elucidation of sensitivity/resistance patterns may provide insights for further treatment refinement.
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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.