Benefit of adjuvant bisphosphonates in early breast cancer treated with contemporary systemic therapy: A meta-analysis of randomized control trials
Bibliographic record
Abstract
Background: The absolute and relative benefits of adjuvant bisphosphonates on disease-free survival and overall survival in patients receiving contemporary systemic therapy for early breast cancer is uncertain. Methods: Data from randomized trials of adjuvant bisphosphonates that recruited patients exclusively after 2000 and reported disease free survival and overall survival was utilized. Five-year disease-free survival and overall survival in bisphosphonates and control group along with associated hazard ratios were extracted. Absolute data were weighted by sample size and hazard ratios were pooled using inverse variance and random effects modelling. Meta-regression comprising linear regression weighted by sample size (mixed effects) was performed to explore association between disease and treatment related factors and absolute differences in benefit from bisphosphonates. Results: Eleven trials comprising 24023 patients were included in the analysis. For disease free survival, pooled hazard ratio was 0.89 (0.81-0.97, p = 0.008) with a 1.5 % weighted mean difference favoring bisphosphonates over control. There was no significant overall survival benefit (0.92, 0.82-1.03, p = 0.16). Among patients receiving anthracycline and taxane based chemotherapy, there were no differences in either disease free survival (0.95, 0.80-1.12) or overall survival (1.04, 0.81-1.32). Meta-regression showed lower benefits in higher risk patients (node-positive, larger tumor size, estrogen receptor-, grade 3 or those receiving chemotherapy). Overall, 1 % (95 % CI 0.75-1.15) of patients experienced osteonecrosis of jaw related to zoledronic acid. Conclusions: Compared to the Early Breast Cancer Trialist's Collaborative Group meta-analysis, benefit from adjuvant bisphosphonates is lower in recent trials especially in higher risk patients receiving contemporary chemotherapy. The balance between benefits and risks of adjuvant bisphosphonates should be considered in individual patients.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.022 | 0.040 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.018 | 0.046 |
| Bibliometrics | 0.004 | 0.004 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| 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".