Role of serum thymidine kinase-1 (TK1) activity in patients (pts) with hormone receptor positive (HR+) advanced breast cancer (ABC) treated with endocrine therapy (ET) in the EFECT trial.
Bibliographic record
Abstract
12031 Background: TK1 plays a critical role in DNA synthesis and cell proliferation. The DiviTum assay measures serum TK1 activity (sTKa), reflecting cancer cell proliferation. Recent studies suggest this assay may provide real time prognostic information in ABC. However, its role in HR+ ABC needs further validation. Methods: EFECT (n = 693) was a double-blind, randomized trial of fulvestrant 250mg versus exemestane after progression on nonsteroidal aromatase inhibitor therapy for ABC. 58% of pts had received > 1 prior ET for ABC. sTKa was retrospectively assessed with DiviTum on serum samples from pts in the EFECT cohort. Samples were collected before start of ET (T0), after 3 (T3) and 6 (T6) months of ET, and at disease progression (PD). Pts were categorized as High/Low sTKa at T0 based on the median value. On-treatment sTKa changes were calculated from T0 to the next available time-point within 3 months from randomization (T3, or PD for those pts with early progression - ePD), accounting for a coefficient of variation of 10%, and defined as follows: Drop (T3 or ePD < T0); Increase (T3 or ePD > T0); No change (T3 or ePD = T0). Analyses were conducted regardless of study arms. Results: All available samples were successfully tested for sTKa (586 samples from 244 consenting pts). Median sTKa at T0 (n = 227), T3 (n = 135), T6 (n = 80) and PD (n = 137) was 97, 57, 57.5 and 132 Du/L, respectively. Median time to progression (mTTP) for pts with Low T0 sTKa (n = 111) was 5.03 months (m) (95% CI 3.91-5.89) vs 2.57 (95% CI 2.04-3.52) for pts with High T0 sTKa (n = 110) (p < 0.001). On-treatment sTKa changes from T0 were analysed in 159 pts (T3 = 116; ePD = 43). mTTP in pts with TK1 Drop (n = 53) was 5.4 m (95% CI 3.7-7.7) vs 3.4 (95% CI 2.1-4.1) in pts with Increase (n = 68) (p < 0.018). mTTP in pts with No change (n = 38) was similar to those with Drop. After adjustment for major prognostic factors, sTKa remained an independent marker. Conclusions: sTKa is a potential circulating prognostic marker in pts with ABC treated with ET, and may represent a tool for upfront identification of ET-resistant pts, and non-invasive monitoring of response to ET. Independent validation of these results is warranted.
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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".