Abstract PS7-30: Differential efficacy, safety and tolerability of low-dose versus standard dose tamoxifen as breast cancer prophylaxis: A network meta-analysis
Bibliographic record
Abstract
Abstract BACKGROUND: Despite reduction in the risk of breast cancer occurrence, the use of prophylactic tamoxifen does not improve longer term outcomes such as survival and comes at the cost of toxicity. As such, chemoprophylaxis is utilized poorly in routine practice. Lower dose tamoxifen has been proposed as a more acceptable alternative for breast cancer prevention. Here, we explore efficacy and treatment-related adverse events (TRAEs) comparing the two tamoxifen dosing regimens in a network meta-analysis. METHOD: We searched PubMed to identify randomized trials (RCTs) of tamoxifen for breast cancer prophylaxis in high-risk patients (as defined in individual trials). Low-dose tamoxifen was defined as less than 20mg per day. We extracted the hazard ratio (HR) for breast cancer events relative to placebo. We also collected data on common and serious TRAE, and calculated odd ratios (OR) for each TRAE relative to placebo. Data were then included in a network meta-analysis comparing low-dose (experimental group) to standard dose tamoxifen (control group). Associations between TRAEs and patient charactericstics were explored using meta-regression which comprised a weighted linear regression using mixed effects modelling. RESULTS: Ten RCTs comprising 35,505 patients were included in the analysis (4 low-dose trials (n=3712 patients) and 6 standard dose trials (n=31,793 patients). There were no significant differences between low-dose and standard dose trials in age (53.3 vs 50.8, p=0.25), post-menopausal status (77.5% vs 49%, p=0.63) or BMI (24.1kg/m2 vs 26.95 kg/m2, p=0.40). Efficacy was similar between the two dosage regimens (HR for breast cancer recurrences: 1.04, 95% CI 0.77-1.41, p=0.78 and for invasive breast cancer: 1.04, 95% CI 0.69-1.56, p=0.85). Differences in TRAEs are shown in the Table. There was a statistically significant reduction in headache with low-dose tamoxifen, and a non-significant reduction in endometrial cancers, other cancers, cardiovascular diseases and all-cause deaths. Hot flashes, vaginal bleeding and endometrial polyps were non-significantly higher with low-dose tamoxifen. In meta-regression analysis, age was associated with lower risk of endometrial carcinoma (p=0.049) and hot flashes (p=0.03). CONCLUSION: The use of prophylactic low-dose tamoxifen provides similar efficacy to standard dosing, but may reduce the risk of certain common and serious TRAEs. TRAEOR95% CIp-valueDeaths0.630.14-2.860.55Endometrial cancer0.320.08-1.240.10Endometrial polyps1.660.84-3.280.15Other cancer0.710.40-1.260.24DVT or PE0.900.12-7.580.93 Coronary heart disease0.720.24-2.150.56Cerebrovascular disease1.600.29-8.970.59Hot flashes1.340.63-2.860.45Vaginal dryness0.840.34-2.030.69Vaginal bleeding1.260.52-3.060.61Vaginal discharge1.080.58-1.990.81Headache0.110.05-0.860.04 Citation Format: Alexandra Desnoyers, Michelle B Nadler, Brooke E Wilson, Eitan Amir. Differential efficacy, safety and tolerability of low-dose versus standard dose tamoxifen as breast cancer prophylaxis: A network meta-analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-30.
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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 | 0.027 | 0.049 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.013 | 0.052 |
| Bibliometrics | 0.004 | 0.004 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".