ReviewFrontiers in oncology2026
Adjuvant endocrine therapy in estrogen-low breast cancer in the era of CDKI: are we at another uncertain crossroads?
Review 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
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Estrogen receptor-low breast cancer is defined as ER expression of 1-10% by immunohistochemistry. It occupies a debated space between luminal and triple-negative disease. The CDK4/6 inhibitors abemaciclib and ribociclib have set new standards for high-risk HR+/HER2-/early breast cancer. However, neither trial stratified patients by ER expression levels. This leaves the ER-low subgroup without dedicated prospective evidence. This review synthesizes data from adjuvant CDK4/6 inhibitor trials, clinical and molecular studies of ER-low BC, biomarker evidence, regulatory context, and chemotherapy/immunotherapy data, with specific attention to the ER-low subgroup and a structured framework for clinical decision-making. ER-low breast cancer is mostly non-luminal (about 75-80% basal-like). Its molecular features, neoadjuvant chemotherapy response rates, and survival outcomes are closer to ER-negative/triple negative breast cancer than ER-high luminal cancer. Both MONARCH E and NATALEE trials enrolled ER-low patients, using the ≥1% positivity threshold. Exploratory subgroup data suggest a numerically consistent benefit from CDK4/6 inhibitors. However, confidence intervals are wide, and formal statistical significance is not shown. PAL trials showed no benefit. This is linked to its specific pharmacology rather than a class effect. CDK4/6 inhibitor activity in ER-low disease appears to result from ER-independent RB pathway mechanisms, CCND1 amplification, and immunomodulatory effects. Frequent RB1 loss, reduced endocrine sensitivity, and cell-cycle control by CDK2/cyclin E counterbalance this activity. ER-low patients who meet high-risk trial eligibility criteria may receive adjuvant CDK4/6 inhibitors when luminal biomarkers support HR+ biology but must be counseled about the evidence gap. Molecular subtyping (PAM50), RB1 assessment, PR status, germline BRCA testing, and multidisciplinary tumor board review are mandatory. Dedicated prospective trials with ER-low as a pre-specified stratum are urgently needed.
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.