Clinical and molecular predictors of sustained response to trastuzumab in metastatic breast cancer
Bibliographic record
Abstract
500 Background: Trastuzumab based chemotherapy has dramatically altered the progression of metastatic breast cancer for patients with HER2/neu positive disease. However, not all patients will have significant response to trastuzumab based chemotherapy. Clinical and molecular predictors are needed to determine who will respond to trastuzumab based chemotherapy. Methods: Patients who received trastuzumab chemotherapy were identified from the BC Cancer Agency Pharmacy Database. Clinical factors were assessed from chart review and database extraction. Immunohistochemical (IHC) analysis was performed using tissue microarray (TMA), and we currently have EGFR, ER status, p53, and MIB-1 stained. We are going to be looking at PTEN, AKT, PR, HER3,and IGF-R as well. Outcomes were defined as sustained response (SR) or no response (NR) Logistic regression analyses were used to evaluate predictive significance of various clinical and IHC factors in outcome. Spearman correlation coefficients were used to determine correlations between factors. Results: We currently have clinical outcome information on 222 patients, and 114 patients with samples suitable for TMA analysis. SR are similar to NR in terms of factors such as disease free interval, estrogen receptor status, age, number of previous lines of chemotherapy and hormonal therapy, and presence or absence of visceral metastases. Patients with grade 2 tumours that were HER2 positive had significantly more sustained responses (45/67, 67%) than those who had grade 3 tumours (64/139, 46%) (p<0.05). We are currently preparing and analyzing tissue by microarray, and this will be presented at ASCO. On the first 75 patients, we have found no significant correlation between EGFR, ER, p53, and MIB-1 with outcome. Patients with positive p53 staining also were more likely to stain for MIB-1. Conclusions: Pathologic grade 2, HER2 positive tumors may have more sustained responses to trastuzumab based treatment than grade 3 tumors. Results on immunohistochemical profiling of 150 tumors treated with trastuzumab will be presented at the ASCO annual meeting. No significant financial relationships to disclose.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 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".