A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment
Why this work is in the frame
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Bibliographic record
Abstract
BACKGROUND: The prognostic significance of germline mutations in BRCA1 and BRCA2 in women with breast cancer remains unclear. A combined analysis was performed to address this uncertainty. METHODS: Two retrospective cohorts of Ashkenazi Jewish women undergoing breast-conserving treatment for invasive cancer between 1980 and 1995 (n = 584) were established. Archived tissue blocks were used as the source of DNA for Ashkenazi Jewish BRCA1/BRCA2 founder mutation analysis. Paraffin-embedded tissue and follow-up information was available for 505 women. RESULTS: Genotyping was successful in 496 women, of whom 56 (11.3%) were found to carry a BRCA1/BRCA2 founder mutation. After a median follow-up period of 116 months, breast cancer specific survival was worse in women with BRCA1 mutations than in those without (62% at 10 years versus 86%; P < 0.0001), but not in women with the BRCA2 mutation (84% versus 86% at 10 years; P = 0.76). Germline BRCA1 mutations were an independent predictor of breast cancer mortality in multivariate analysis (hazard ratio 2.4, 95% confidence interval 1.2-4.8; P = 0.01). BRCA1 status predicted breast cancer mortality only among women who did not receive chemotherapy (hazard ratio 4.8, 95% confidence interval 2.0-11.7; P = 0.001). The risk for metachronous ipsilateral cancer was not greater in women with germline BRCA1/BRCA2 founder mutations than in those without mutations (P = 0.68). CONCLUSION: BRCA1 mutations, but not BRCA2 mutations, are associated with reduced survival in Ashkenazi women undergoing breast-conserving treatment for invasive breast cancer, but the poor prognosis associated with germline BRCA1 mutations is mitigated by adjuvant chemotherapy. The risk for metachronous ipsilateral disease does not appear to be increased for either BRCA1 or BRCA2 mutation carriers, at least up to 10 years of follow up.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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) | 0.000 | 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