Bibliographic record
Abstract
Aromatase inhibitors (AIs) have been approved as second-line treatment for estrogen receptor-positive (ER+) metastatic breast cancer after first-line treatment with the selective estrogen receptor modulator (SERM) tamoxifen. Anastrozole and letrozole have also recently been widely approved as first-line endocrine therapy for postmenopausal women with hormone receptor-positive metastatic breast cancer. The three third-generation selective oral AIs approved for use in the United States include two nonsteroidal agents, anastrozole (Arimidex) and letrozole (Femara), and the irreversible steroidal inhibitor exemestane (Aromasin). Several major ongoing clinical trials with a variety of treatment regimens are comparing the relative efficacy of tamoxifen with the steroidal and nonsteroidal AIs in the adjuvant setting. The first strategy compares an AI against tamoxifen directly. Among these are the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial (anastrozole), the BIG FEMTA (Femara-Tamoxifen Breast International Group) trial (letrozole), and the EXEM and TEAM (exemestane) trials. A second strategy is examining the use of an AI as an extension after the initial 5 years of tamoxifen. Examples of this trial design are the MA-17 (letrozole) and the National Surgical Adjuvant Breast and Bowel Project (NSABP B-33, exemestane) trials. A third approach is the use of these agents in sequence with tamoxifen as therapy within the initial 5 postoperative years. Examples of this approach are the International Collaboration Cancer Group trial (tamoxifen for 2-3 years followed by either tamoxifen or exemestane for the remainder of the 5-year period), the BIG FEMTA trial (patients are crossed over from tamoxifen to Ietrozole or letrozole to tamoxifen), and the Arimidex-Nolvadex (ARNO) trial (patients receiving tamoxifen are randomized either to continue with tamoxifen or to switch to anastrozole). A single trial is comparing tamoxifen and anastrozole as initial 5-year therapy, or a combination of the two. The study addressing this design is the ATAC trial. Finally, a small trial in Norway is comparing 2 years of an AI versus a placebo in very low-risk patients with receptor-positive breast tumors. Most adjuvant trials have companion studies associated with the main protocol. These are to determine the end-organ effects of the inhibitors and include measurements of quality of life, bone and lipid metabolism, and endometrial effects. This review addresses the clinical implications of these studies of AIs.
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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 | 0.008 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.003 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".