ArticleNature cancer2021
Serial single-cell genomics reveals convergent subclonal evolution of resistance as early-stage breast cancer patients progress on endocrine plus CDK4/6 therapy.
Article in Nature cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02712723 (Femara), which is not on this map. Cited by 65 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Femara (Letrozole) Plus Ribociclib (LEE011) or Placebo as Neo-adjuvant Endocrine Therapy for Women With ER-positive, HER2-negative Early Breast Cancer
Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- CDK4/6 inhibitors as conditional immune-priming agents in breast cancer: therapeutic windows, sequencing strategies, and rational combinations with immunotherapy, radiotherapy, and antibody-drug conjugates.Frontiers in immunology · 2026Pooled it
- Multimodal assessment of exceptional responders refines subtyping-directed precision treatment in HR+/HER2- breast cancer.The Journal of clinical investigation · 2026Trial
- Palbociclib and endocrine therapy diminish adaptive anti-tumor immunity in early breast cancer: The NeoRHEA phase 2 study.Nature communications · 2025Trial
- Continuous versus Standard Palbociclib Treatment and Molecular Profiling of Solid Tissues and Liquid Biopsies in the CCTG MA.38 Trial in Advanced Breast Cancer.Cancer research communications · 2025Trial
- Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Trial
- Integrative pipeline to profile and target endocrine therapy-insensitive cell populations in ER+ breast cancer.bioRxiv : the preprint server for biology · 2026Article
- Evolutionary Antifragile Therapy Is a Treatment Strategy to Suppress Drug Resistance by Exploiting Dose-Response Convexity.Cancer research · 2026Article
- Tumor evolution: signaling pathways, molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Understanding and Overcoming Antibody-Drug Conjugate Resistance: Biological Mechanisms and Emerging Analytical Frameworks in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- ScSpTITH: a rank-correlation framework for robust quantification of multi-dimensional tumor heterogeneity.Human genetics · 2026Article
- Serial Spatial Transcriptomics Reveal Divergent Routes to Therapy Resistance in Metastatic Breast Cancer.Research square · 2026Article
- CRISPR activation screens identify oncogenic lncRNAs that are susceptible to CDK4/6 inhibitor treatment.Nature communications · 2026Article
- Article
- Loss of luminal lineage drives resistance to next-generation ERα antagonists in pretreated ERNature communications · 2026Article
- The ADAPT learning cancer treatment system: ARPA-H's initiative to revolutionize cancer therapy.Cancer cell · 2026Article
- Deciphering Cell Cycle Dynamics and Cell States in Single-cell RNA-seq data with SPAE.bioRxiv : the preprint server for biology · 2026Article
- Emerging clinical applications of exosomes in breast cancer management from biomarkers to therapeutics.Discover oncology · 2026Review
- Molecular and cellular composition changes after neoadjuvant letrozole and palbociclib in early luminal breast cancer.Cell reports. Medicine · 2026Article
- Cyclin-dependent kinase 4 and 6 inhibitors and the breast cancer immune ecosystem: immune remodeling, resistance, and therapeutic reprogramming.Frontiers in immunology · 2026Review
- Computational decoding of cell-cycle phase effects on cancer hallmarks across breast cancer subtypes.Breast cancer research : BCR · 2025Article
5 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
18 authors at 9 institutions in 2 countries.
Funding
Abstract
Combining cyclin-dependent kinase (CDK) inhibitors with endocrine therapy improves outcomes for metastatic estrogen receptor positive (ER+) breast cancer patients but its value in earlier stage patients is unclear. We examined evolutionary trajectories of early-stage breast cancer tumors, using single cell RNA sequencing (scRNAseq) of serial biopsies from the FELINE clinical trial (#NCT02712723) of endocrine therapy (letrozole) alone or combined with the CDK inhibitor ribociclib. Despite differences in subclonal diversity evolution across patients and treatments, common resistance phenotypes emerged. Resistant tumors treated with combination therapy showed accelerated loss of estrogen signaling with convergent up-regulation of JNK signaling through growth factor receptors. In contrast, cancer cells maintaining estrogen signaling during mono- or combination therapy showed potentiation of CDK4/6 activation and ERK upregulation through ERBB4 signaling. These results indicate that combination therapy in early-stage ER+ breast cancer leads to emergence of resistance through a shift from estrogen to alternative growth signal-mediated proliferation.
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What OpenQuestion holds
Registered trials
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.