Iter-4360dd15-0110-transcript
第 110 轮执行轨迹
→ call search_memory({"limit":8,"query":"4360dd15 BOLERO-2 PMID 22149876 primary endpoint NEJM"}) → call list_recent({"n":8})
→ call list_by_tag({"limit":8,"tag":"4360dd15"})
【tool:search_memory】
{"ok": true, "results": [{"title": "Iter-4360dd15-0060-transcript", "tags": "iteration transcript", "modified": "20260424200117000", "preview": "!! 第 60 轮执行轨迹
→"}, {"title": "Iter-4360dd15-0094-transcript", "tags": "iteration transcript", "modified": "20260424210844000", "preview": "!! 第 94 轮执行轨迹 → call search_m"}, {"title": "Iter-4360dd15-0090-transcript", "tags": "iteration transcript", "modified": "20260424210019000", "preview": "!! 第 90 轮执行轨迹 【tool:list_recent】
{"ok": true, "items": [{"title": "Iter-4360dd15-0109-reflection", "modified": "20260424214413000", "tags": "iteration reflection"}, {"title": "NEXT_FOCUS", "modified": "20260424214413000", "tags": "pinned focus"}, {"title": "先判定证据层级，再找精确 PMID", "modified": "20260424214413000", "tags": "lesson evidence-chain trial-screening metadata-first"}, {"title": "Iter-4360dd15-0109-transcript", "modified": "20260424214407000", "tags": "iteration transcript"}, {"title": "PMID 22149876 is the original BOLERO-2 phase 3 primary report, not 24267730", "modified": "20260424214401000", "tags": "fact method 4360dd15 clinical-trials evidence-chain"}, {"title": "Iter-4360dd15-0108-reflection", "modified": "20260424214200000", "tags": "iteration reflection"}, {"title": "亚组论文不能当原始试验", "modified": "20260424214200000", "tags": "lesson evidence-chain trial-screening"}, {"title": "Iter-4360dd15-0108-transcript", "modified": "20260424214156000", "tags": "iteration transcript"}]}
【tool:list_by_tag】
{"ok": true, "items": [{"title": "PMID 22149876 is the original BOLERO-2 phase 3 primary report, not 24267730", "modified": "20260424214401000"}, {"title": "PMID 24267730 is a subgroup analysis, not the first original human trial", "modified": "20260424214147000"}, {"title": "Iter-4360dd15-0106-four-candidate-audit", "modified": "20260424213752000"}, {"title": "Iter-4360dd15-0104-three-remaining-candidates-are-not-original-first-reports", "modified": "20260424213638000"}, {"title": "Iter-4360dd15-0103-EuropePMC-38310895-reference-parser-and-candidate-shortlist", "modified": "20260424213315000"}, {"title": "Iter-4360dd15-0100-human-trial-vs-non-original-screening-of-38310895-references", "modified": "20260424212530000"}, {"title": "Iter-4360dd15-0099-critic-mechanistic-vs-aging-trial", "modified": "20260424212312000"}, {"title": "Iter-4360dd15-0098-EuropePMC-extract-human-trial-PMIDs", "modified": "20260424212055000"}]}
→ call pubmed_search({"limit":10,"query":"BOLERO-2 everolimus exemestane phase 3 primary endpoint Lancet 2012"})
→ call web_search({"limit":10,"query":"BOLERO-2 everolimus exemestane primary endpoint PubMed 22149876"})
→ call web_search({"limit":10,"query":"\"22149876\" BOLERO-2 primary endpoint"})
【tool:pubmed_search】
{"ok": true, "query": "BOLERO-2 everolimus exemestane phase 3 primary endpoint Lancet 2012", "results": []}
【tool:web_search】
{"ok": true, "query": "BOLERO-2 everolimus exemestane primary endpoint PubMed 22149876", "results": [{"title": "Everolimus plus exemestane for hormone-receptor-positive, human ...", "url": "https://www.annalsofoncology.org/article/S0923-7534(19)36905-4/fulltext", "snippet": "The BOLERO-2 study previously demonstrated that adding everolimus (EVE) to exemestane (EXE) significantly improved progression-free survival (PFS) by more than twofold in patients with hormone-receptor-positive (HR +), HER2-negative advanced breast cancer that recurred or progressed during/after treatment with nonsteroidal aromatase inhibitors (NSAIs). The overall survival (OS) analysis is ..."}, {"title": "Everolimus in Postmenopausal Hormone-Receptor-Positive Advanced Breast ...", "url": "https://www.nejm.org/doi/full/10.1056/NEJMoa1109653", "snippet": "In this phase 3, randomized trial, we compared everolimus and exemestane versus exemestane and placebo (randomly assigned in a 2:1 ratio) in 724 patients with hormone-receptor-positive advanced ..."}, {"title": "The BOLERO-2 trial: the addition of everolimus to exemestane ... - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/22764762/", "snippet": "Research has indicated that aberrant signaling through the mTOR pathway is associated with resistance to endocrine therapies. The BOLERO-2 trial examined the effects on progression-free survival of the addition of everolimus to exemestane in a patient population of postmenopausal, hormone receptor-positive, a
【tool:web_search】
{"ok": true, "query": "\"22149876\" BOLERO-2 primary endpoint", "results": [{"title": "ORBi: Detailled Reference", "url": "https://orbi.uliege.be/handle/2268/224448?locale=en", "snippet": "N Engl J Med. 2012; 366 (6): 520-529. doi: 10.1056/NEJMoa1109653 22149876 Yardley DA, Noguchi S, Pritchard KI, Everolimus plus exemestane in postmenopausal patients with HR (+) breast cancer: BOLERO-2 final progression-free survival analysis."}]}
→ call web_fetch({"max_chars":4000,"url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1109653"})
【tool:web_fetch】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://www.nejm.org/doi/full/10.1056/NEJMoa1109653'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
→ call web_search({"limit":10,"query":"\"NEJMoa1109653\" PubMed"})
→ call web_search({"limit":10,"query":"\"Everolimus in Postmenopausal Hormone-Receptor-Positive Advanced Breast Cancer\" PubMed"})
→ call web_search({"limit":10,"query":"\"everolimus plus exemestane\" \"progression-free survival\" \"22149876\""})
【tool:web_search】
{"ok": true, "query": "\"NEJMoa1109653\" PubMed", "results": [{"title": "(PDF) Everolimus in Postmenopausal Hormone-Receptor-Positive Advanced ...", "url": "https://www.researchgate.net/publication/51860286_Everolimus_in_Postmenopausal_Hormone-Receptor-Positive_Advanced_Breast_Cancer", "snippet": "Everolimus in Postmenopausal Hormone-Receptor-Positive Advanced Breast Cancer December 2011 New England Journal of Medicine 366 (6):520-9 DOI: 10.1056/ NEJMoa1109653 Source PubMed Authors: José ..."}, {"title": "PDF Supplementary Appendix - The New England Journal of Medicine", "url": "https://www.nejm.org/doi/suppl/10.1056/NEJMoa1109653/suppl_file/nejmoa1109653_appendix.pdf", "snippet": "Supplement to: Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-posi-tive advanced breast cancer. N Engl J Med 2012;366:520-9. DOI: 10.1056/ NEJMoa1109653 ."}]}
【tool:web_search】
{"ok": true, "query": "\"Everolimus in Postmenopausal Hormone-Receptor-Positive Advanced Breast Cancer\" PubMed", "results": []}
【tool:web_search】
{"ok": true, "query": "\"everolimus plus exemestane\" \"progression-free survival\" \"22149876\"", "results": []}
→ call web_search({"limit":10,"query":"\"Everolimus in Postmenopausal Hormone-Receptor-Positive Advanced Breast Cancer\" primary endpoint progression-free survival"})
→ call web_search({"limit":10,"query":"\"BOLERO-2\" \"primary endpoint\" PFS local investigator review"})
→ call web_search({"limit":10,"query":"\"NEJMoa1109653\" progression-free survival local investigator review"})
【tool:web_search】
{"ok": true, "query": "\"Everolimus in Postmenopausal Hormone-Receptor-Positive Advanced Breast Cancer\" primary endpoint progression-free survival", "results": []}
【tool:web_search】
{"ok": true, "query": "\"BOLERO-2\" \"primary endpoint\" PFS local investigator review", "results": []}
【tool:web_search】
{"ok": true, "query": "\"NEJMoa1109653\" progression-free survival local investigator review", "results": []}
→ call write_note({"tags":["fact","knowledge","4360dd15","clinical-trials","evidence-chain"],"text":"!! 结论\nBOLERO-2 的原始 III 期主报告对应 PMID 22149876，题名为 ''Everolimus in Postmenopausal Hormone-Receptor-Positive Advanced Breast Cancer''，发表于 ''N Engl J Med'' 2012;366:520-529，DOI 10.1056/NEJMoa1109653。\n\n!! 可引用证据链\n# DuckDuckGo 检索结果直接把 22149876 与 NEJM 主报告并列在一起（ORBi 题录页）：[[https://orbi.uliege.be/handle/2268/224448?l)
【tool:write_note】
{"ok": true, "path": "C:\\Users\\yh599\\Documents\\GitHub\\LLM-yh\\Sisyphus\\wiki\\tiddlers\\BOLERO-2_原始主报告_PMID_22149876_与_primary_endpoint_PFS.tid", "title": "BOLERO-2 原始主报告 PMID 22149876 与 primary endpoint PFS"}
【assistant】
已完成本轮最窄子任务：把 BOLERO-2 原始主报告的 PMID 和主要终点锁定下来，并写入长期记忆。
要点：
- 原始 III 期主报告：PMID 22149876
- 题名：*Everolimus in Postmenopausal Hormone-Receptor-Positive Advanced Breast Cancer*
- 期刊：*N Engl J Med* 2012;366:520-529
- DOI：10.1056/NEJMoa1109653
- primary endpoint：progression-free survival (PFS)，摘要线索还指出按 local investigator review 评估
已排除：
- 22764762：综述/解读
- 24267730：老年亚组分析
<NEXT_FOCUS>用可访问的第二独立来源再确认 BOLERO-2 主报告的 PMID 22149876 与 primary endpoint PFS，并尽量补一个不依赖 NEJM 403 的题录页或 PubMed/PMC 证据链。</NEXT_FOCUS>
```