Protective Effect of Estrogen (E2) and Increased Risk of E2 Plus Progestin (Prog) on Breast Cancer (BrCa). The 2009 Review of the Women's Health Initiative (WHI) Hormone Replacement Therapy (HRT) Published Trials.
Bibliographic record
Abstract
Abstract INTRODUCTION & METHODOLOGY.The objective of this review is to identify from the two WHI published randomized HRT trials the BrCa risk or benefit, with a special focus on different impact of E2-alone vs E2+Prog on human breast carcinogenesis (BrCa-genesis).In the 1st trial (JAMA 2002, 2007), healthy women age 50 - 79 were randomized to E2 plus Prog versus placebo (Plac). Reviewed were Hazard ratios (HRs) for all pts and also for those with or without prior Hormone use. Mean follow up was 5.2 years.In the 2nd trial (JAMA 2004, 2006), women with hysterectomy age 50 - 79 were randomized to E2 alone (without Prog) versus Plac. Mean follow up was 7.1 years. Reviewed were all pts, and also subsets with or without prior E2 or Prog; with or without prior history of Benign Breast Disease (PHBrD); and with or without prior history of a 1st degree relative with BrCa (PH1stRelBrCa).RESULTS.Invasive BrCa incidence:N (%)HR95% C.I.1st TrialAll participants:16,608 (100%)1.260.83 - 1.97No prior Hormone use:12,304 (74.1%)1.060.81 - 1.38Prior Hormone use <5 yrs:3,005 (18.1%)2.131.15 - 3.94*Prior Hormone use 5 - 10 yrs:783 (4.7%)4.611.01 - 21.02*2nd TrialAll participants:10,739 (100%)0.800.62 - 1.04No prior hormone use:5,763 (53.7%)0.650.46 - 0.92*Prior E2 use:4,976 (46.3%)0.980.67 - 1.44Prior E2 + PROG use:468 (4.4%)2.350.60 - 9.14No PHBrD:7,681 (71.5%)0.570.41 - 0.78*No PH1stRelBrCa8,554 (80.0%)0.680.50 - 0.92*CONCLUSION:1. Results from the 1st trial show that concomitant use of E2 with Prog, particularly in women with prior Hormone use, is associated with increased BrCa hazards.2. The results of the 2nd HRT trial indicate that use of HRT with E2 alone is associated with a reduction in BrCa incidence, significant in the majority of women with no prior BrCa risk factors. Also the results show that prior Prog but not prior E2 elevate the risk.3. These data indicate that HRT with E2 alone has a BrCa protective effect, while adding Prog increases the risk.4. These results are also compatible with a dual E2 effect on BrCa-genesis, where exogenous E2 are protective, but endogenous E2 [endE2] are carcinogenic, as shown from decades of anti-end E2 research with Tamoxifen, oophorectomy or Aromatase inhibitors.5. Based on these data we propose that in women with hysterectomy and no prior history of risk factors, the use of HRT with E2 alone as chemoprevention is plausible, and needs urgent verification.* significance, "p" <0.05. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 908.
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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 | 0.005 | 0.012 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.003 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".