Association Between Human Epidermal Growth Factor Receptor 2-Low Status and Time to Development of Brain Metastases Among Patients With Breast Cancer: A Retrospective Cohort Study
Bibliographic record
Abstract
PURPOSE Human epidermal growth factor receptor 2 (HER2)-low is a newly defined subgroup of HER2-negative breast cancer. It is unknown whether HER2-low status is associated with brain metastases (BrM) development. We aimed to determine the association between HER2-low status and the time to developing BrM. METHODS HER2 status was determined in a cohort of 689 women with metastatic breast cancer (MBC) who underwent treatment for BrM at Sunnybrook Odette Cancer Centre from 2008 to 2018. In patients with primary breast cancer (PBC) HER2 subclassification available (subgroup 1), we investigated time from PBC diagnosis to BrM diagnosis (PBC-time to brain metastases [TTBM]). In patients with HER2 subclassification available in any tissue (subgroup 2), we investigated time from MBC diagnosis to BrM diagnosis (MBC-TTBM). RESULTS In subgroup 1 (n = 175), patients with HER2-low disease (n = 42) had a shorter PBC-TTBM compared with those with HER2-zero disease (n = 77; hazard ratio, 2.4; P = .0003). When stratified by hormone receptor (HR) status, this observation held true in the HR+/HER2– population, but not in the triple-negative breast cancer (TNBC) population. In subgroup 2 (n = 279), patients with HER2-low disease (n = 53) had a shorter MBC-TTBM compared to those with HER2-zero disease (n = 44) in the HR+/HER2– population (hazard ratio, 1.55; P = .036); however, this did not hold true in the TNBC population. Likelihood ratio test revealed significant interaction between HER2 and HR status in subgroup 2 ( P = .016), but not subgroup 1 ( P = .21). CONCLUSION Our findings suggest that among patients with HR+ breast cancer, HER2-low status was associated with shorter TTBM compared with HER2-zero status. In a subset of patients for whom HER2 status of the PBC was available, HER2-low status was associated with shorter PBC-TTBM, irrespective of HR status. This study suggests a previously unrecognized association between HER2-low status and timing of BrM development.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 teacher head, 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".