Iter-4360dd15-0112-transcript
第 112 轮执行轨迹
→ call search_memory({"limit":10,"query":"4360dd15 BOLERO-2 PMID 22149876 primary endpoint PFS second independent authoritative source"})【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 → call read_note({"title":"NEXT_FOCUS"})
→ call read_note({"title":"BOLERO-2 原始主报告 PMID 22149876 与 primary endpoint PFS"})
→ call list_recent({"n":8})
【tool:read_note】
{"ok": true, "title": "NEXT_FOCUS", "tags": "pinned focus", "text": "!! 下轮焦点（来自 mission 4360dd15 · Iter-0110）\n\n找到一个不依赖 NEJM 403 的第二独立权威来源，直接复核 PMID 22149876 与 primary endpoint=PFS。"}
【tool:read_note】
{"ok": true, "title": "BOLERO-2 原始主报告 PMID 22149876 与 primary endpoint PFS", "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?locale=en\n# NEJM 页面标题显示为原始随机 III 期试验：https://www.nejm.org/doi/full/10.1056/NEJMoa1109653（本环境抓取受 403 限制，但题名/摘要片段已由检索结果提供）\n# 检索摘要明确写出试验设计：\"In this phase 3, randomized trial, we compared everolimus and exemestane versus exemestane and placebo...\"，支持其为原始试验而非综述/亚组。\n\n!! 主要终点\nBOLERO-2 的 primary endpoint 为 ''progression-free survival (PFS)''，检索摘要还提示评估方式为 ''local investigator review''。\n\n!! 排除项\n# 22764762：综述/试验解读，不是主报告。\n# 24267730：老年亚组分析，不是主报告。\n\n!! 备注\n当前证据已经足以把 BOLERO-2 原始人类试验的准确 PMID 和 primary endpoint 锁定为上面两项；后续如需更严谨，可再补一条可访问题录或 PMCID 页面作为第二独立来源。"}
【tool:list_recent】
{"ok": true, "items": [{"title": "Error-20260425-054541", "modified": "20260424214541000", "tags": "error iteration"}, {"title": "Iter-4360dd15-0110-reflection", "modified": "20260424214532000", "tags": "iteration reflection"}, {"title": "NEXT_FOCUS", "modified": "20260424214532000", "tags": "pinned focus"}, {"title": "题录线索也要做双源闭环", "modified": "20260424214532000", "tags": "lesson evidence-chain trial-screening metadata-first"}, {"title": "Iter-4360dd15-0110-transcript", "modified": "20260424214528000", "tags": "iteration transcript"}, {"title": "BOLERO-2 原始主报告 PMID 22149876 与 primary endpoint PFS", "modified": "20260424214522000", "tags": "fact knowledge 4360dd15 clinical-trials evidence-chain"}, {"title": "Iter-4360dd15-0109-reflection", "modified": "20260424214413000", "tags": "iteration reflection"}, {"title": "先判定证据层级，再找精确 PMID", "modified": "20260424214413000", "tags": "lesson evidence-chain trial-screening metadata-first"}]}
→ call pubmed_search({"limit":5,"query":"22149876 BOLERO-2 everolimus exemestane progression-free survival"})
→ call web_search({"limit":5,"query":"BOLERO-2 ClinicalTrials.gov primary outcome progression-free survival PMID 22149876"})
→ call web_search({"limit":5,"query":"PMID 22149876 BOLERO-2 primary endpoint PFS independent source"})
【tool:pubmed_search】
{"ok": true, "query": "22149876 BOLERO-2 everolimus exemestane progression-free survival", "results": [{"pmid": "39118946", "title": "The role of everolimus in metastatic breast cancer and possibilities of moving forward-a narrative review.", "source": "Ann Transl Med", "pubdate": "2024 Aug 1", "authors": ["Rubovszky G"], "url": "https://pubmed.ncbi.nlm.nih.gov/39118946/"}, {"pmid": "38904918", "title": "BOLERO-5: a phase II study of everolimus and exemestane combination in Chinese post-menopausal women with ER + /HER2- advanced breast cancer.", "source": "Discov Oncol", "pubdate": "2024 Jun 21", "authors": ["Shao ZM", "Cai L", "Wang S", "Hu X", "Shen K", "Wang H", "Li H", "Feng J"], "url": "https://pubmed.ncbi.nlm.nih.gov/38904918/"}, {"pmid": "37183684", "title": "Evaluating everolimus for the treatment of breast cancer.", "source": "Expert Opin Pharmacother", "pubdate": "2023 May-Aug", "authors": ["Moreau-Bachelard C", "Robert M", "Gourmelon C", "Bourbouloux E", "Patsouris A", "Frenel JS", "Campone M"], "url": "https://pubmed.ncbi.nlm.nih.gov/37183684/"}, {"pmid": "34740541", "title": "Real-World Outcomes of Everolimus and Exemestane for the Treatment of Metastatic Hormone Receptor-Positive Breast Cancer in Patients Previously Treated With CDK4/6 Inhibitors.", "source": "Clin Breast Cancer", "pubdate": "2022 Feb", "authors": ["Mo H", "Renna CE", "Moore HCF", "Abraham J", "Kruse ML", "Montero AJ", "LeGrand SB", "Wang L"], "url": "https://pubmed.ncbi.nlm.nih.gov/34740541/"},
【tool:web_search】
{"ok": true, "query": "BOLERO-2 ClinicalTrials.gov primary outcome progression-free survival PMID 22149876", "results": [{"title": "Study Details | NCT00863655 - ClinicalTrials.gov", "url": "https://clinicaltrials.gov/study/NCT00863655", "snippet": "Prevalence of ESR1 Mutations in Cell- Free DNA and Outcomes in Metastatic Breast Cancer: A Secondary Analysis of the BOLERO-2 Clinical Trial. JAMA Oncol. 2016 Oct 1;2 (10):1310-1315. doi: 10.1001/jamaoncol.2016.1279."}, {"title": "Everolimus in Postmenopausal Hormone-Receptor-Positive Advanced Breast ...", "url": "https://www.nejm.org/doi/full/10.1056/NEJMoa1109653", "snippet": "Everolimus combined with an aromatase inhibitor improved progression-free survival in patients with hormone-receptor-positive advanced breast cancer previously treated with nonsteroidal ..."}, {"title": "Everolimus in Postmenopausal Hormone-Receptor-Positive Advanced Breast ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5705195/", "snippet": "The BOLERO-2 study showed that the addition of everolimus to exemestane significantly improves progression-free survival , with observed medians of 6.9 and 2.8 months, corresponding to a 57% reduction in the hazard ratio."}, {"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
【tool:web_search】
{"ok": true, "query": "PMID 22149876 BOLERO-2 primary endpoint PFS independent source", "results": [{"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": "Checking your browser - reCAPTCHA - PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/22149876/", "snippet": "Everolimus combined with an aromatase inhibitor improved progression-free survival in patients with hormone-receptor-positive advanced breast cancer previously treated with nonsteroidal aromatase inhibitors. (Funded by Novartis; BOLERO-2 ClinicalTrials.gov number, NCT00863655.)."}, {"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 Plus Exemestane in Postmenopausal P
→ call web_fetch({"max_chars":5000,"url":"https://pubmed.ncbi.nlm.nih.gov/22149876/"})
→ call web_fetch({"max_chars":6000,"url":"https://clinicaltrials.gov/study/NCT00863655"})
→ call web_fetch({"max_chars":4000,"url":"https://ascopubs.org/doi/10.1200/jco.2013.31.26_suppl.152"})
【tool:web_fetch】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://pubmed.ncbi.nlm.nih.gov/22149876/'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
【tool:web_fetch】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://clinicaltrials.gov/study/NCT00863655'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
【tool:web_fetch】
{"ok": false, "error": "Client error '403 Forbidden' for url 'https://ascopubs.org/doi/10.1200/jco.2013.31.26_suppl.152'\nFor more information check: https://developer.mozilla.org/en-US/docs/Web/HTTP/Status/403"}
→ call web_search({"limit":5,"query":"BOLERO-2 primary endpoint PFS local investigator review review article PMC"})
【tool:web_search】
{"ok": true, "query": "BOLERO-2 primary endpoint PFS local investigator review review article PMC", "results": [{"title": "Everolimus plus exemestane as first-line therapy in HR +, HER2 − ...", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3907668/", "snippet": "The primary endpoint of BOLERO-2 was investigator -assessed PFS (defined as time from randomization to first documented progression or death from any cause) per Response Evaluation Criteria in Solid Tumors (RECIST), v1.0."}, {"title": "Everolimus Plus Exemestane in Postmenopausal Patients with HR+ Breast ...", "url": "https://escholarship.org/uc/item/0715f3jd", "snippet": "Methods BOLERO-2 is a phase 3, double-blind, randomized, international trial comparing everolimus (10 mg/day) plus exemestane (25 mg/day) versus placebo plus exemestane in postmenopausal women with HR (+) advanced BC with recurrence/progression during or after NSAIs. The primary endpoint was PFS by local investigator review , and was confirmed by independent central radiology review . Overall ..."}, {"title": "Everolimus plus exemestane for hormone-receptor-positive, human ...", "url": "https://www.sciencedirect.com/science/article/pii/S0923753419369054", "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
→ call web_fetch({"max_chars":6000,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3907668/"})
→ call web_fetch({"max_chars":6000,"url":"https://escholarship.org/uc/item/0715f3jd"})
→ call web_fetch({"max_chars":4000,"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5705195/"})
【tool:web_fetch】
{"ok": true, "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3907668/", "status": 200, "content_type": "text/html; charset=utf-8", "text": "Everolimus plus exemestane as first-line therapy in HR+, HER2− advanced breast cancer in BOLERO-2 - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites. Search Log in Dashboard Publications Account settings Log out Search… Search NCBI Primary site navigation Search Logged in as: Dashboard Publications Account settings Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide PERMALINK Copy As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice Breast Cancer Res Treat . 2013 Dec 21;143(3):459–467. doi: 10.1007/s10549-013-2814-5 Search in PMC Search in PubMed View in NLM Catalog Add to search Everolimus plus exemestane as first-line therapy in HR + , HER2 − advanced breast cancer in BOLERO-2 J Thaddeus Beck J Thaddeus Beck 1 Highlands Oncology Group, 3232 N. North Hills Blvd
【tool:web_fetch】
{"ok": true, "url": "https://escholarship.org/uc/item/0715f3jd", "status": 202, "content_type": "text/html; charset=UTF-8", "text": "", "truncated": false}
【tool:web_fetch】
{"ok": true, "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5705195/", "status": 200, "content_type": "text/html; charset=utf-8", "text": "Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites. Search Log in Dashboard Publications Account settings Log out Search… Search NCBI Primary site navigation Search Logged in as: Dashboard Publications Account settings Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide PERMALINK Copy As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice N Engl J Med . Author manuscript; available in PMC: 2017 Nov 28. Published in final edited form as: N Engl J Med. 2011 Dec 7;366(6):520–529. doi: 10.1056/NEJMoa1109653 Search in PMC Search in PubMed View in NLM Catalog Add to search Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer José Baselga José Baselga , M.D., Ph.D. 1 Ma
→ call web_search({"limit":10,"query":"\"22149876\" BOLERO-2 PMID review primary endpoint PFS PMCID"})
【tool:web_search】
{"ok": true, "query": "\"22149876\" BOLERO-2 PMID review primary endpoint PFS PMCID", "results": [{"title": "Efficacy and toxicity of everolimus plus exemestane in third and later ...", "url": "https://jsurgmed.com/article/view/745731", "snippet": "PMID : 22149876 ; PMCID : PMC5705195. Royce M, Bachelot T, Villanueva C, Özgüroglu M, Azevedo SJ, Cruz FM, et al. Everolimus Plus Endocrine Therapy for Postmenopausal Women With Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: A Clinical Trial."}, {"title": "Journal of Surgery and Medicine » Submission » Efficacy and toxicity of ...", "url": "https://dergipark.org.tr/en/pub/josam/article/745731", "snippet": "Epub 2011 Dec 7. PMID : 22149876 ; PMCID : PMC5705195. 19. Royce M, Bachelot T, Villanueva C, Özgüroglu M, Azevedo SJ, Cruz FM, et al. Everolimus Plus Endocrine Therapy for Postmenopausal Women With Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: A Clinical Trial."}]}
→ call write_note({"tags":["fact","knowledge","4360dd15","clinical-trials","evidence-chain"],"text":"!! 结论\n用一个非 NEJM 页面、可直接抓取的第二独立来源复核后，BOLERO-2 的原始主报告仍然可稳定指向 PMID 22149876，且其 primary endpoint 仍是 PFS。\n\n!! 复核来源 1：PMC 综述/分析文章\nhttps://pmc.ncbi.nlm.nih.gov/articles/PMC3907668/\n文章正文直接写明：\"The primary endpoint of BOLERO-2 was investigator-assessed PFS...\"\n这说明 BOLERO-2 的核心终点定义不是后验推断，而是被后续独立文章在正文中明确复述。\n\n!!)
【tool:write_note】
{"ok": true, "path": "C:\\Users\\yh599\\Documents\\GitHub\\LLM-yh\\Sisyphus\\wiki\\tiddlers\\BOLERO-2_PMID_22149876_的第二独立复核来源与_primary_endpoint.tid", "title": "BOLERO-2 PMID 22149876 的第二独立复核来源与 primary endpoint"}
【assistant】
本轮完成：我用一个**非 NEJM 直接页**的独立 PMC 来源，复核了 BOLERO-2 的两件事：
- **PMID 22149876** 仍对应原始主报告
- **primary endpoint = PFS**，且文中写作 **investigator-assessed PFS**
我已把结果沉淀到记忆里：**“BOLERO-2 PMID 22149876 的第二独立复核来源与 primary endpoint”**。
本轮新增的可复用结论是：
**临床试验证据链不必死盯原始 DOI 页；只要能找到一篇独立 PMC/综述/后续分析在正文中明确复述 trial design + primary endpoint，就能作为第二权威复核源。**
<NEXT_FOCUS>再找一条与 BOLERO-2 无直接隶属关系的独立权威来源，专门复核“22149876 = 原始主报告”而不是只复核终点。</NEXT_FOCUS>
```