ArticleFrontiers in oncology2026
Integrated CDK4/6 inhibitor resistance and primary-metastatic discordance in hormone receptor-positive/HER2-negative metastatic breast cancer: a translational framework focused on invasive ductal carcinoma with gastric metastasis.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: CDK4/6 inhibitors have reshaped treatment for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer, but resistance frequently emerges and may interact with metastatic phenotypic evolution. We developed an integrated resistance-discordance framework and explored its clinical interpretability in invasive ductal carcinoma (IDC) with gastric metastasis. Methods: Public MSK-INK4 (cBioPortal study ID: breast_ink4_msk_2021) and MBCproject (brca_mbcproject_wagle_2017) cohorts were curated for HR+/HER2-negative disease. A five-module CDK4/6 inhibitor resistance score (0-5) was constructed from predefined mutation and copy-number events. In MBCproject RNA-seq samples, single-sample gene-set enrichment analysis quantified proliferation and estrogen-response activity. Discordance burden was defined as z(proliferation score) minus z(ER score), using primary tumors as the reference. Three institutional IDC gastric-metastasis cases were projected onto the framework for interpretability but not inferential testing. Results: Seventy HR+/HER2-negative MBCproject samples and 1116 deduplicated MSK-INK4 metastatic samples were analyzed. MBCproject metastases had higher resistance scores than primary tumors (P = 0.001), whereas metastatic scores were similar between MBCproject and MSK-INK4 (P = 0.202). Metastases showed higher proliferation activity (P = 0.014) and a trend toward lower ER activity (P = 0.071). The high-resistance/high-discordance quadrant was enriched for PI3K-axis events (OR = 16.52; P = 0.034), chromatin-remodeling loss-of-function events (OR = 12.47; P = 0.001), and cell-cycle/RB-axis events (OR = 9.03; P = 0.001). Among the three IDC gastric-metastasis cases, two available gastric NGS profiles mapped to predefined resistance modules, and the case with increased gastric Ki-67 showed the strongest IHC-adapted discordance and projected toward the high-resistance/high-discordance phenotype. Conclusion: Coupling resistance-associated genomic events with metastatic phenotype discordance may provide a clinically interpretable lens for HR+/HER2-negative metastatic breast cancer and for rare IDC gastric-metastasis presentations.
Indexed as
Identifiers
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.