Prognosis and Biological Characteristics of ER-Low Metastatic Breast Cancer: Results from a Multicenter Cohort and the TONIC Trial
Bibliographic record
Abstract
PURPOSE: The purpose of this study was to assess prognosis of estrogen receptor (ER)-low expression and its dynamics in HER2- metastatic breast cancer and to compare sensitivity to nivolumab between ER-low and triple-negative breast cancer (TNBC). EXPERIMENTAL DESIGN: Two cohorts were analyzed: a multicenter cohort of 982 patients with HER2- metastatic breast cancer and one prospective cohort of 110 patients with ER <10%/HER2- metastatic breast cancer enrolled in the TONIC trial (testing nivolumab). Endpoints were overall survival (OS) and post-relapse survival (PRS) in the retrospective cohort and progression-free survival, OS, and clinical benefit rate in the TONIC trial. RESULTS: A total of 7.3% of retrospective cases had ER-low breast cancer, 15 of 110 of the TONIC trial. In the retrospective cohort, patients with ER-low breast cancer had significantly poorer OS (P < 0.001) and numerically shorter PRS (P = 0.230) compared with ER+/HER2- breast cancer and numerically longer OS (P = 0.098) and significantly longer PRS (P = 0.017) compared with TNBC. In the TONIC trial, patients with ER-low breast cancer, compared with TNBC, showed similar response to nivolumab (clinical benefit rate: 20.0% vs. 22.1%; P = 1), progression-free survival (median, 1.7 vs. 2.0 months; P = 0.5), and OS (median, 5.3 vs. 8.6 months; P = 0.3). Among patients with primary ER+/HER2- breast cancer (n = 565), the conversion toward ER-low breast cancer or TNBC at metastasis conferred independent negative prognostic impact both for OS (P = 0.002 and P = 0.001, respectively) and PRS (P = 0.018 and P = 0.001, respectively). CONCLUSIONS: We provided evidence of the prognostic role of ER-low expression and its dynamics in patients with HER2- metastatic breast cancer. We offered insights into sensitivity to anti-PD1 in metastatic breast cancer, showing that patients with ER-low breast cancer have comparable likelihood of responding to nivolumab as those with TNBC.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".