Triple-negative receptor status and prognosis in the NCIC CTG MA. 21 adjuvant breast cancer trial
Bibliographic record
Abstract
550 Background: Triple-negative breast tumors which are negative for ER, PR, and HER2-neu receptors by immunohistochemistry are associated with a poor prognosis. The MA.21 trial compared 3 adjuvant chemotherapy regimens after surgery in pre- or early menopausal women 60 years or younger with breast cancer (Proceedings ASCO 2007, 25, 550). This analysis explored the outcome of the triple-negative subset of patients compared to nontriple negatives in the MA.21 trial with respect to relapse-free survival (RFS). Methods: Women with axillary node-positive or high-risk node-negative breast cancer were randomized to cyclophosphamide, epirubicin, 5FU (CEF), dose-dense epirubicin and cyclophosphamide plus filgrastim followed by paclitaxel (EC/T) or doxorubicin and cyclophosphamide followed by paclitaxel (AC/T), for six months. ER status was a known stratification factor for all patients. Median follow-up was 30.4 months with 261 recurrences. Characteristics of patients with and without knowledge of triple-negative status were compared with exact Fisher's tests. Step-wise multivariate Cox regressions were performed with forced inclusion of trial therapy and stratification factors. Additionally, RFS was determined from adjusted Cox survivor plots. Results: The trial enrolled 2,104 patients. ER, PR, and HER2 status based on local institutional results were known for 1,623; 551 patients had triple-negative tumors. After adjusting for treatment, stratification factors of lymph node status, surgery type, and age, highly significant differences in 3-year RFS were found when the triple-negative subgroup (RFS 80.5%) was compared to others where all PR and HER2-neu had known values (RFS 86.5%, p=0.0002), or not (RFS 87.7%, p< 0.0001). From multivariate analyses, triple-negative patients had significantly worse RFS (p< 0.0001). At this time, there are too few events to assess whether RFS differs by treatment arm for triple-negative patients. Conclusions: Pre- and postmenopausal women with triple-negative tumors had a reduced three-year relapse-free survival compared to women with nontriple-negative tumors. Supported by NCIC Canada and Canadian Cancer Society, Pfizer, Bristol-Myers Squibb, Amgen, Janssen Ortho, Ortho Biotech, and NCI US. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Aventis, Biomira, Ortho Biotech, Pfizer, Pharmacia, Roche, YM Biosciences AstraZeneca, Aventis, Pfizer, Pharmacia AstraZeneca, Aventis
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".