Targeting IGF-IR improves neoadjuvant chemotherapy efficacy in breast cancers with low IGFBP7 expression
Why this work is in the frame
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Bibliographic record
Abstract
There has been a long-standing interest in targeting the type 1 insulin-like growth factor receptor (IGF-1R) signaling system in breast cancer due to its key role in neoplastic proliferation and survival. However, no IGF-1R targeting agent has shown substantial clinical benefit in controlled phase 3 trials, and no biomarker has been shown to have clinical utility in the prediction of benefit from an IGF-1R targeting agent. IGFBP7 is an atypical insulin-like growth factor binding protein as it has a higher affinity for the IGF-1R than IGF ligands. We report that low IGFBP7 gene expression identifies a subset of breast cancers for which the addition of ganitumab, an anti-IGF-1R monoclonal antibody, to neoadjuvant chemotherapy, substantially improved the pathological complete response rate compared to neoadjuvant chemotherapy alone. The pCR rate in the chemotherapy plus ganitumab arm was 46.9% in patients in the lowest quartile of IGFBP7 expression, in contrast to only 5.6% in the highest quartile. Furthermore, high IGFBP7 expression predicted increased distant metastasis risk. If our findings are confirmed, decisions to halt the development of IGF-1R targeting drugs, which were based on disappointing results of prior trials that did not use predictive biomarkers, should be reviewed.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.000 | 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 it