Neoadjuvant Chemotherapy Plus Denosumab Compared to Chemotherapy Alone in Hormonal Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Premenopausal Breast Cancer Patients
Bibliographic record
Abstract
Background: High mRNA expression levels of receptor activator of nuclear factor-kB (RANK) were linked with several adverse prognostic factors in breast cancer. The present study aims to assess the activity of neoadjuvant chemotherapy combined with denosumab compared to chemotherapy alone in premenopausal patients with hormonal receptors (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Methods: In this single-center randomized phase II study, we enrolled patients with ER Allred score 4 - 8 at diagnostic biopsy with locally advanced either inoperable tumors or tumors that need downsizing to allow for breast conservative surgery (BCS). Enrolled patients were randomized to receive either neoadjuvant chemotherapy (four cycles of epirubicin/doxorubicin with cyclophosphamide and four cycles of docetaxel) with denosumab or the same chemotherapy alone. Patients in the experimental arm received subcutaneous denosumab 120 mg starting with the first chemotherapy cycle and then with every other cycle (total of four doses). Residual cancer burden (RCB) was the primary endpoint. Results: We recruited 50 patients (26 in control arm, 24 in experimental arm) for the study. Baseline characteristics were balanced between the two arms including age at diagnosis, ER Allred score (≤ 6 vs. > 6), progesterone receptor (PR) status, Ki67 level, clinical T, clinical N, and clinical stage (stage II vs. III). Noteworthy, 86% of patients were node-positive, 44% had cT4 tumors and 80% had ER Allred score > 6. Two patients in the control arm did not undergo breast surgery (one lost to follow-up, the other had local progression). There was no difference in the rates of BCS (58.3% in both arms) between the two arms. No difference in RCB between control and experimental arms (RCB 0-1: 25% vs. 20.8%, respectively, P = 0.73) was found. Similarly, there were no differences in pathological T stage (pT0-1: 87.5% vs. 70.8%, P = 0.29), pathological N stage (N0: 41.7% vs. 29.2%, P = 0.55) or pathological stage (41.6% vs. 33.3%, P = 0.75). No significant difference in adverse events profiles between the two arms was observed. Conclusions: Adding denosumab to neoadjuvant chemotherapy was not associated with lower RCB or improved pathological stage in premenopausal HR+/HER2-negative breast cancer patients with comparable rate of BCS. No new safety signals were observed with the addition of denosumab.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".