Response: Re: Hormone Therapy and the Risk of Breast Cancer in BRCA1 Mutation Carriers
Bibliographic record
Abstract
The model proposed by Eisinger and Huiart ( 1 ) is intriguing but is complex and will prove difficult to confirm. We should remember that the modification of the effect of ovarian hormones on cancer risk by age of exposure is not restricted to breast cancer or to women at high risk for the disease. For example, oral contraceptives are associated with a reduced risk of endometrial cancer, but estrogen hormone replacement therapy is a risk factor. Oral contraceptives are also associated with a reduced risk of ovarian cancer, but again hormone replacement is a risk factor ( 2 ). At least three possible explanations exist for these relationships: 1) different drugs and different doses, 2) different effects of exogenous hormones in women with and without endogenous circulating estrogens, and 3) age-specific effects, that is, hormone exposure is associated with latent and prolonged reduced risk in young women but with increased short-term risk in older women. However, regarding the first point, the formulations for oral contraceptives and hormone replacement therapies are actually more similar than dissimilar, and the associations of oral contraceptives with reduced cancer risk do not appear to differ by formulation ( 3 ). Regarding the second point, the study of young women with early surgical menopause would be informative. Regarding the third point, if estrogen exposure were to advance the clinical presentation of a preexisting cancer or a precancerous lesion, and if the rate of tumor growth was rapid, then we would expect to see an adverse effect among current users and a rapid decline in risk after cessation of therapy. This expectation appears to be true for breast cancer ( 4 ), but in breast cancer, the situation is complex because of the mix of hormone receptor–positive and hormone receptor–negative tumors. We have previously reported that in contrast to the association of hormone therapy with reduced breast cancer risk observed in postmenopausal women in this study, the use of oral contraceptives was associated with increased breast cancer risk among young BRCA1 mutation carriers ( 5 ). The third scenario is the most plausible, and it is premature to search for genetic factors that divide women into being susceptible or not susceptible to an increased breast cancer risk when using hormone therapy.
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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 | 0.002 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.016 | 0.005 |
| Insufficient payload (model declined to judge) | 0.020 | 0.007 |
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".