2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/2iy5wruuedsh6.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/00yc7rcvua6a7.js","/_next/static/immutable/chunks/37ktb71aq3480.js","/_next/static/immutable/chunks/2d50b-7eu4558.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/2d6noqpp6ehas.js","/_next/static/immutable/chunks/1sx186c93bpzg.js","/_next/static/immutable/chunks/3dc-1n866s65i.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2w1bvggzb0ga8.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T67f,(Z)-endoxifen is the tamoxifen metabolite that possesses the highest affinity to the estrogen receptor and is evolving as an alternative to tamoxifen. Mammographic breast density (MBD) change has been shown to be a proxy for tamoxifen therapy response. The objective was to measure the effect of 2 different doses of (Z)-endoxifen on MBD, safety, and side effects in healthy women. Healthy premenopausal women included in the national Swedish screening program in Stockholm were invited to KARISMA Endoxifen, a proof of principle, dose determining, double-blinded, randomized, placebo-controlled trial. Women were randomly assigned to placebo or 1 or 2 mg of (Z)-endoxifen daily for 6 months. In all, 240 women were randomly assigned. There was a significant relative change in MBD in both (Z)-endoxifen arms compared to placebo: -19.3% (95% confidence interval [CI] = -6.15% to -32.4%) in the 1 mg arm and -26.5% (95% CI = -14.1% to -38.9%) in the 2 mg arm. The number of participants discontinuing because of adverse events related to the investigational medicinal product was 4 (placebo), 5 (1 mg), and 11 (2 mg), respectively. Participants on 2 mg of (Z)-endoxifen reported significantly higher scores of vasomotor symptoms, compared with placebo. No clinically significant changes in hematological safety tests or vital signs were noted. Both 1 and 2 mg of (Z)-endoxifen significantly reduced MBD to a degree comparable to the established 20 mg dose of tamoxifen. The 1 mg dosage of (Z)-endoxifen indicated superior tolerability. Future studies are necessary to confirm impact on breast cancer incidence. ClinicalTrials.gov ID: NCT05068388.31:T9a7,Abstract Background (Z)-endoxifen is the tamoxifen metabolite that possesses the highest affinity to the estrogen receptor and is evolving as an alternative to tamoxifen. Mammographic breast density (MBD) change has been shown to be a proxy for tamoxifen therapy response. The objective was to measure the effect of 2 different doses of (Z)-endoxifen on MBD, safety, and side effects in healthy women. Methods Healthy premenopausal women included in the national Swedish screening program in Stockholm were invited to KARISMA Endoxifen, a proof of principle, dose determining, double-blinded, randomized, placebo-controlled trial. Women were randomly assigned to placebo or 1 or 2 mg of (Z)-endoxifen daily for 6 months. Results In all, 240 women were randomly assigned. There was a significant relative change in MBD in both (Z)-endoxifen arms compared to placebo: −19.3% (95% confidence interval [CI] = −6.15% to −32.4%) in the 1 mg arm and −26.5% (95% CI = −14.1% to −38.9%) in the 2 mg arm. The number of participants discontinuing because of adverse events related to the investigational medicinal product was 4 (placebo), 5 (1 mg), and 11 (2 mg), respectively. Participants on 2 mg of (Z)-endoxifen reported significantly higher scores of vasomotor symptoms, compared with placebo. No clinically significant changes in hematological safety tests or vital signs were noted. Conclusion Both 1 and 2 mg of (Z)-endoxifen significantly reduced MBD to a degree comparable to the established 20 mg dose of tamoxifen. The 1 mg dosage of (Z)-endoxifen indicated superior tolerability. Future studies are necessary to confirm impact on breast cancer incidence. Trial Registration ClinicalTrials.gov ID: NCT05068388. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"tamoxifen: generic Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on tamoxifen (generic). Clinician-written summaries and actionable practice insights. Updated daily.\",\"url\":\"https://www.reachrx.ai/hub/tag/generic/tamoxifen\",\"breadcrumb\":{\"@type\":\"BreadcrumbList\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https://www.reachrx.ai\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Research Hub\",\"item\":\"https://www.reachrx.ai/hub\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Generics\",\"item\":\"https://www.reachrx.ai/hub/tag/generic\"},{\"@type\":\"ListItem\",\"position\":4,\"name\":\"tamoxifen\",\"item\":\"https://www.reachrx.ai/hub/tag/generic/tamoxifen\"}]}}"}}]],["$","$L2f",null,{"title":"tamoxifen: Research & Clinical Takeaways","description":"Explore research on tamoxifen (generic) — efficacy, safety, and comparative data.","papers":[{"doi":"10.1136/bmj-2026-100216","pmid":"42580772","title":"Evidence based interventions for bipolar disorder across phases and age groups: living umbrella review, evaluation, analysis, and communication hub (U-REACH) project","journal_title":"BMJ","journal_issn":"1756-1833","published_at":"2026-08-11T00:00:00.000Z","url":"https://doi.org/10.1136/bmj-2026-100216","source_score":89,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-17T13:33:30.432Z","updated_at":"2026-08-17T13:33:30.432Z","tags":[{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"brand","value":"Caplyta","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"brand","value":"Latuda","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"brand","value":"Vraylar","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"category","value":"Medicine, General & Internal","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"condition","value":"Bipolar Disorder","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"aripiprazole","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"asenapine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"carbamazepine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"cariprazine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"divalproex","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"fluoxetine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"haloperidol","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"ketamine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"lamotrigine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"lithium","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"lumateperone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"lurasidone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"olanzapine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"paliperidone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"quetiapine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"risperidone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"tamoxifen","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"valproate","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"generic","value":"ziprasidone","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Atypical Antipsychotic","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Brain Stimulation","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Mood Stabilizer","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"NMDA Receptor Antagonist","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Nutraceutical","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"modality","value":"Psychosocial Intervention","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"sample_size","value":"n=77","value_numeric":77},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"study_design","value":"Umbrella Review (Living Systematic Review with Meta-Analyses)","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"warning","value":"Study design label 'Umbrella Review' is a non-standard design category; it is a higher-order synthesis above standard systematic reviews and meta-analyses.","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"warning","value":"Tamoxifen is listed as effective for adult mania — this is an uncommon clinical use (PKC inhibition mechanism) and may surprise readers unfamiliar with this evidence base.","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"warning","value":"The 'practice_changing' impact flag is applied because this is a comprehensive living umbrella review with an open-access clinical decision tool, though individual treatment effect sizes are not extractable from the abstract alone.","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100216","tag_type":"warning","value":"The sample_size tag reflects the number of included systematic reviews (n=77), not individual patient-level N, which is not reported as a single aggregate in the abstract.","value_numeric":null}],"summaries":{"what_studied":"A living umbrella review (U-REACH) evaluated the certainty of evidence for pharmacological, nutraceutical, psychosocial, brain stimulation, and circadian rhythm-based treatments across all bipolar disorder phases (depression, mania/mixed, maintenance) and age groups (adults; children/adolescents), using 77 systematic reviews (21 network meta-analyses, 56 pairwise meta-analyses) published up to November 2024.","key_result":"Across 2,510 meta-analyses covering 133 outcomes and 116 unique treatments, GRADE ratings were high (n=236), moderate (n=827), low (n=986), and very low (n=461). Agents effective across multiple phases in adults included aripiprazole, asenapine, cariprazine, divalproex/valproate, lamotrigine, lithium, olanzapine, paliperidone, quetiapine, and risperidone; in youth, lurasidone and olanzapine-fluoxetine were supported for bipolar depression, and aripiprazole, asenapine, olanzapine, quetiapine, and risperidone for mania.","limitations":"Most evidence is rated low or very low certainty (1,447 of 2,510 meta-analyses), limiting confidence in many treatment estimates; the umbrella review design inherits limitations of the included meta-analyses (e.g., heterogeneity, publication bias); pediatric data are sparse compared with adult data.","practice_takeaway":"Use the freely available EBI-BD platform (ebibd-database.org) to identify phase- and age-specific evidence-based options and discuss patient-preferred safety profiles using its 12-intervention, 17-outcome preference tool. For cross-phase adult coverage, lithium, quetiapine, olanzapine, aripiprazole, and divalproex/valproate have the broadest support; for youth, lurasidone (bipolar depression) and aripiprazole (mania) have the strongest pediatric evidence."}},{"doi":"10.1016/j.breast.2026.104887","pmid":"42520573","title":"Evolution of male breast cancer treatment: Results from twenty years of BreastSurgANZ Quality Audit data","journal_title":"The Breast","journal_issn":"0960-9776","published_at":"2026-07-24T00:00:00.000Z","url":"https://doi.org/10.1016/j.breast.2026.104887","source_score":6,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-09T13:24:59.510Z","updated_at":"2026-08-09T13:24:59.510Z","tags":[{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"category","value":"Obstetrics & Gynecology","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"condition","value":"Breast Cancer","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"condition","value":"Male Breast Cancer","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"generic","value":"aromatase inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"generic","value":"tamoxifen","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"modality","value":"Adjuvant Chemotherapy","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"modality","value":"Endocrine Therapy","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"modality","value":"Mastectomy","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"modality","value":"Sentinel Lymph Node Biopsy","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"sample_size","value":"n=258246","value_numeric":258246},{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"study_design","value":"Registry-Based Observational Study","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"warning","value":"Male breast cancer numbers (n=1,542 over 20 years) are small relative to females (n=256,704), which may limit detection of modest treatment changes in the male cohort.","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"warning","value":"Reference list entries were not rendered in the source text, so specific citations supporting key claims cannot be verified.","value_numeric":null},{"paper_doi":"10.1016/j.breast.2026.104887","tag_type":"warning","value":"The study is observational and registry-based; causality cannot be inferred from treatment trend differences between decades.","value_numeric":null}],"summaries":{"what_studied":"This bi-national registry study used the BreastSurgANZ Quality Audit (BQA) database to compare demographic, histological, and treatment data for male vs. female breast cancer patients in Australia and New Zealand over two decades (2003–2012 vs. 2013–2022), covering 258,246 patients (1,542 males, 256,704 females).","key_result":"Male breast cancer treatment was largely static over 20 years — the only significant change was increased sentinel lymph node biopsy (SLNB) uptake (66% vs. 47%, p<0.001). By contrast, female patients saw significant shifts in nearly every treatment domain; adjuvant chemotherapy use fell in females over time (OR 1.10, 95% CI 1.10–1.11, p<0.001 favoring the earlier decade), while it remained stable in males.","limitations":"- BQA relies on surgical teams to record adjuvant therapies, so post-surgical treatments (e.g., chemotherapy referred but not yet started) may be undercounted.\n- Observational design over a wide time span introduces potential unmeasured biases.\n- Male breast cancer numbers are small (n=1,542), limiting statistical power for subgroup analyses.","practice_takeaway":"Male breast cancer treatment in Australia and New Zealand has barely changed over 20 years — SLNB adoption is the main advance, while surgical and adjuvant therapy de-escalation seen in females has not occurred in males. Clinicians should be aware that male patients are managed without sex-specific evidence-based guidelines, and extrapolation from female data may not be appropriate."}},{"doi":"10.1001/jamasurg.2026.2340","pmid":"42384406","title":"Lumpectomy Margins and Local Recurrence in DCIS","journal_title":"JAMA Surgery","journal_issn":"2168-6254","published_at":"2026-07-01T00:00:00.000Z","url":"https://doi.org/10.1001/jamasurg.2026.2340","source_score":14,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-08T13:26:25.410Z","updated_at":"2026-07-08T13:26:25.410Z","tags":[{"paper_doi":"10.1001/jamasurg.2026.2340","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2340","tag_type":"brand","value":"Arimidex","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2340","tag_type":"category","value":"Surgery","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2340","tag_type":"condition","value":"Ductal Carcinoma In Situ","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2340","tag_type":"generic","value":"anastrozole","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2340","tag_type":"generic","value":"tamoxifen","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2340","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2340","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2340","tag_type":"modality","value":"Aromatase Inhibitor","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2340","tag_type":"modality","value":"Lumpectomy","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2340","tag_type":"modality","value":"Selective Estrogen Receptor Modulator","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2340","tag_type":"modality","value":"Whole-Breast Irradiation","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2340","tag_type":"sample_size","value":"n=3104","value_numeric":3104},{"paper_doi":"10.1001/jamasurg.2026.2340","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2340","tag_type":"study_design","value":"Ancillary Analysis of Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2340","tag_type":"warning","value":"Level of evidence assigned as 2 (high-quality RCT data source), but the ancillary nature of this analysis may warrant downgrading in some evidence hierarchies.","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2340","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the conclusion supporting omission of re-excision for close margins, but the adjusted analysis showed a non-significant HR — clinicians should weigh the unadjusted vs. adjusted findings carefully.","value_numeric":null},{"paper_doi":"10.1001/jamasurg.2026.2340","tag_type":"warning","value":"This is an ancillary (post-hoc) analysis of NSABP B-35, not a pre-specified primary endpoint; subgroup sample sizes are smaller and results should be interpreted with caution.","value_numeric":null}],"summaries":{"what_studied":"This ancillary analysis of the NSABP B-35 phase 3 RCT examined whether lumpectomy margin width (thresholds of 1 mm and 2 mm) affected ipsilateral breast tumor recurrence (IBTR) in 3,104 postmenopausal women with HR-positive DCIS who received whole-breast irradiation (WBI) plus adjuvant tamoxifen or anastrozole (enrolled 2003–2006; median follow-up sufficient for 10-year cumulative incidence reporting).","key_result":"IBTR occurred in 3.3% overall (90/2,707). At 10 years, unadjusted IBTR was 5.6% vs 4.0% for margins <1 mm vs ≥1 mm (P = .04), and 5.3% vs 3.8% for margins <2 mm vs ≥2 mm (P = .05). After adjusting for patient and tumor factors, margin width was **not** a significant predictor of IBTR (2-mm threshold HR 1.33; 95% CI, 0.86–2.06).","limitations":"- This is an ancillary (not pre-specified primary) analysis of a trial not powered for margin-width subgroups, limiting inferential strength.\n- All patients had tumor-free margins and received WBI plus endocrine therapy; results may not apply to those omitting radiation or endocrine therapy.\n- Findings are restricted to postmenopausal women with HR-positive DCIS, so generalizability to premenopausal or HR-negative DCIS patients is uncertain.","practice_takeaway":"For postmenopausal women with HR-positive DCIS treated with lumpectomy, WBI, and endocrine therapy, the absolute IBTR difference between close (<1 mm or <2 mm) and wider margins is small and margin width loses significance after adjustment — clinicians can consider forgoing re-excision for close margins in appropriate patients. Decisions should still account for individual patient and tumor factors."}},{"doi":"10.1038/s41375-026-03013-1","pmid":"42350604","title":"Role of endothelial Dlc1 in embryonic vascular development and adult bone marrow hematopoiesis","journal_title":"Leukemia","journal_issn":"0887-6924","published_at":"2026-06-25T00:00:00.000Z","url":"https://doi.org/10.1038/s41375-026-03013-1","source_score":8,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-03T13:38:46.964Z","updated_at":"2026-07-03T13:38:46.964Z","tags":[{"paper_doi":"10.1038/s41375-026-03013-1","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41375-026-03013-1","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1038/s41375-026-03013-1","tag_type":"condition","value":"Bone Marrow Failure","value_numeric":null},{"paper_doi":"10.1038/s41375-026-03013-1","tag_type":"condition","value":"Hematopoietic Stem Cell Niche Dysfunction","value_numeric":null},{"paper_doi":"10.1038/s41375-026-03013-1","tag_type":"condition","value":"Vascular Developmental Defect","value_numeric":null},{"paper_doi":"10.1038/s41375-026-03013-1","tag_type":"generic","value":"tamoxifen","value_numeric":null},{"paper_doi":"10.1038/s41375-026-03013-1","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1038/s41375-026-03013-1","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1038/s41375-026-03013-1","tag_type":"modality","value":"Rho GTPase-Activating Protein Modulation","value_numeric":null},{"paper_doi":"10.1038/s41375-026-03013-1","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41375-026-03013-1","tag_type":"study_design","value":"Preclinical Animal Study","value_numeric":null},{"paper_doi":"10.1038/s41375-026-03013-1","tag_type":"warning","value":"No sample size is explicitly reported for the single-cell RNA sequencing experiment in the supplementary text; n values cited (e.g., Control n=31, Dlc1EC-KO n=19) apply only to the CBC/flow cytometry cohort.","value_numeric":null},{"paper_doi":"10.1038/s41375-026-03013-1","tag_type":"warning","value":"Study design tag 'Preclinical Animal Study' is used as this is a mouse genetics study; no standard canonical label fully captures the combined embryonic/adult conditional knockout design.","value_numeric":null},{"paper_doi":"10.1038/s41375-026-03013-1","tag_type":"warning","value":"This is a supplementary methods/data document — the main results figures and quantitative outcome data (exact n per group, effect sizes for most endpoints) are in the primary paper and not fully reproduced here; some numerical claims are drawn from the abstract only.","value_numeric":null}],"summaries":{"what_studied":"This study evaluated the role of the Rho GTPase-activating protein Dlc1 in bone marrow endothelial cells (ECs), using endothelial-specific constitutive and inducible (Cdh5-CreERT2) Dlc1 knockout mouse models to examine effects on embryonic vasculogenesis, adult bone marrow vascular architecture, and hematopoietic stem and progenitor cell (HSPC) support.","key_result":"Constitutive endothelial Dlc1 deletion caused embryonic lethality with severe vascular defects. In adult mice, inducible EC-specific Dlc1 deletion disrupted bone marrow vascular architecture and significantly reduced multipotent hematopoietic progenitors and myeloid-lineage cells. Single-cell RNA sequencing showed transcriptional reprogramming of Dlc1-deficient ECs, with disrupted expression of key niche signals (Kitl, Cxcl12, Pdgfb) and impaired EC-to-HSPC ligand-receptor communication; hematopoietic cells showed transcriptional features of metabolic stress and reduced biosynthetic activity.","limitations":"- No randomization or investigator blinding was applied during group allocation, introducing potential bias.\n- Sample sizes were not predetermined by power calculations.\n- Findings are in mouse models only; translational relevance to human bone marrow failure or hematologic disease is inferred but not directly tested.","practice_takeaway":"Dlc1 in bone marrow endothelial cells is essential for maintaining the vascular niche that supports normal hematopoiesis; endothelial dysfunction via loss of Dlc1 impairs HSPC output. This positions endothelial Rho GTPase signaling as a potential target to explore in bone marrow failure syndromes and hematologic diseases."}},{"doi":"10.1200/jco-26-00841","pmid":"42218652","title":"Low-Dose Tamoxifen in Noninvasive Breast Neoplasia: Long-Term Results From an Individual-Participant Data Pooled Analysis","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-05-31T00:00:00.000Z","url":"https://doi.org/10.1200/jco-26-00841","source_score":56,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-04T18:18:10.121Z","updated_at":"2026-08-04T18:18:10.121Z","tags":[{"paper_doi":"10.1200/jco-26-00841","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1200/jco-26-00841","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1200/jco-26-00841","tag_type":"condition","value":"Ductal Carcinoma In Situ","value_numeric":null},{"paper_doi":"10.1200/jco-26-00841","tag_type":"condition","value":"High-Risk Breast Lesions","value_numeric":null},{"paper_doi":"10.1200/jco-26-00841","tag_type":"condition","value":"Microinvasive Breast Carcinoma","value_numeric":null},{"paper_doi":"10.1200/jco-26-00841","tag_type":"generic","value":"tamoxifen","value_numeric":null},{"paper_doi":"10.1200/jco-26-00841","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1200/jco-26-00841","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1200/jco-26-00841","tag_type":"modality","value":"Selective Estrogen Receptor Modulator","value_numeric":null},{"paper_doi":"10.1200/jco-26-00841","tag_type":"sample_size","value":"n=1545","value_numeric":1545},{"paper_doi":"10.1200/jco-26-00841","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1200/jco-26-00841","tag_type":"study_design","value":"Pooled Analysis (Individual Participant Data)","value_numeric":null},{"paper_doi":"10.1200/jco-26-00841","tag_type":"warning","value":"Menopausal status subgroup analyses (especially contralateral breast cancer in premenopausal women) are secondary endpoints and should be interpreted with caution.","value_numeric":null},{"paper_doi":"10.1200/jco-26-00841","tag_type":"warning","value":"The 'impact_flag' of practice_changing is applied based on the magnitude of benefit and explicit author support for dose de-escalation, but regulatory approval of low-dose tamoxifen for this indication varies by region.","value_numeric":null},{"paper_doi":"10.1200/jco-26-00841","tag_type":"warning","value":"The pooled analysis includes three studies with potentially different designs and patient populations; between-study variability was addressed statistically but may still influence results.","value_numeric":null}],"summaries":{"what_studied":"Individual-participant pooled analysis of 3 clinical studies evaluating low-dose tamoxifen (5 mg daily or 10 mg every other day for 2–5 years) versus control in 1,545 women with ER-positive or unknown DCIS, microinvasive carcinoma, or high-risk breast lesions, over a median follow-up of 9.4 years.","key_result":"In postmenopausal women, low-dose tamoxifen cut breast cancer events nearly in half vs. controls (40/335 vs. 93/401; HR 0.51, 95% CI 0.35–0.73; 10-year absolute risk reduction 11.2%). In premenopausal women, no significant overall reduction was seen (HR 0.90, 95% CI 0.70–1.17), though contralateral breast cancer was reduced (HR 0.45, 95% CI 0.26–0.76). Serious adverse events were infrequent and similar between groups.","limitations":"- Pooled analysis of only 3 studies with potential between-study heterogeneity, despite mixed-effects modelling.\n- Premenopausal subgroup findings for contralateral breast cancer are based on a subset, limiting precision.\n- Included women with ER-unknown lesions, which may dilute effect estimates.","practice_takeaway":"For postmenopausal women with DCIS or high-risk breast lesions, low-dose tamoxifen (5 mg/day) offers a meaningful and durable risk reduction with a favorable safety profile — consider it as a dose de-escalation alternative to standard 20 mg dosing. In premenopausal women, the overall benefit is less clear, though contralateral breast cancer protection appears real."}},{"doi":"10.1093/jsxmed/qdag120","pmid":"42134684","title":"Evaluation of a combination of off-label PDE5 inhibitor and tamoxifen in acute Peyronie’s disease","journal_title":"The Journal of Sexual Medicine","journal_issn":"1743-6095","published_at":"2026-05-14T00:00:00.000Z","url":"https://doi.org/10.1093/jsxmed/qdag120","source_score":40,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-17T13:21:44.054Z","updated_at":"2026-05-17T13:21:44.054Z","tags":[{"paper_doi":"10.1093/jsxmed/qdag120","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1093/jsxmed/qdag120","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1093/jsxmed/qdag120","tag_type":"condition","value":"Peyronie's Disease","value_numeric":null},{"paper_doi":"10.1093/jsxmed/qdag120","tag_type":"generic","value":"tamoxifen","value_numeric":null},{"paper_doi":"10.1093/jsxmed/qdag120","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1093/jsxmed/qdag120","tag_type":"modality","value":"PDE5 Inhibitor","value_numeric":null},{"paper_doi":"10.1093/jsxmed/qdag120","tag_type":"modality","value":"Selective Estrogen Receptor Modulator","value_numeric":null},{"paper_doi":"10.1093/jsxmed/qdag120","tag_type":"sex","value":"male","value_numeric":null},{"paper_doi":"10.1093/jsxmed/qdag120","tag_type":"warning","value":"Full text of this paper was not provided — only the citation metadata is available. Summary fields reflecting numerical results and specific study design details (e.g., sample size, comparator, randomization) could not be verified or extracted. Key result and limitations are partially inferred from context.","value_numeric":null},{"paper_doi":"10.1093/jsxmed/qdag120","tag_type":"warning","value":"Study design (e.g., RCT vs. observational) and level of evidence could not be determined from the available information.","value_numeric":null},{"paper_doi":"10.1093/jsxmed/qdag120","tag_type":"warning","value":"The specific PDE5 inhibitor used is not named in the provided metadata; brand and generic tags could not be applied.","value_numeric":null}],"summaries":{"what_studied":"This study evaluated the combination of an off-label PDE5 inhibitor and tamoxifen in men with acute Peyronie's disease, assessing efficacy and safety outcomes during the active inflammatory phase.","key_result":"The paper's full numerical results are not available in the provided abstract, but the study examined whether the combination regimen produced measurable improvements in penile curvature, plaque size, pain, or erectile function in the acute phase of Peyronie's disease.","limitations":"The study uses off-label drug combinations, which may limit generalizability; the acute phase of Peyronie's disease is inherently variable and may complicate outcome attribution. Full text data were not provided, limiting extraction of specific numbers.","practice_takeaway":"Clinicians managing acute Peyronie's disease may consider this combination as an investigational option, but should note the off-label status of the PDE5 inhibitor in this context and await full outcome data before changing practice."}},{"doi":"10.1093/jnci/djag087","pmid":"42070780","title":"Endoxifen for mammographic density reduction—results from the KARISMA endoxifen trial","journal_title":"JNCI: Journal of the National Cancer Institute","journal_issn":"0027-8874","published_at":"2026-05-04T00:00:00.000Z","url":"https://doi.org/10.1093/jnci/djag087","source_score":86,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-07","doi":"10.1093/jnci/djag087","days":"7","issn":"0027-8874","rank":"1","field":"Clinical Medicine","score":"86","category":"Oncology","categories":["Oncology"],"_categories":["Oncology"]},"pubmed":{"doi":"10.1093/jnci/djag087","title":"Endoxifen for mammographic density reduction-results from the KARISMA endoxifen trial.","journal":"Journal of the National Cancer Institute","methods":"","results":"In all, 240 women were randomly assigned. There was a significant relative change in MBD in both (Z)-endoxifen arms compared to placebo: -19.3% (95% confidence interval [CI] = -6.15% to -32.4%) in the 1 mg arm and -26.5% (95% CI = -14.1% to -38.9%) in the 2 mg arm. The number of participants discontinuing because of adverse events related to the investigational medicinal product was 4 (placebo), 5 (1 mg), and 11 (2 mg), respectively. Participants on 2 mg of (Z)-endoxifen reported significantly higher scores of vasomotor symptoms, compared with placebo. No clinically significant changes in hematological safety tests or vital signs were noted.","abstract":"$30","keywords":[],"pubmed_id":"42070780","conclusions":"Both 1 and 2 mg of (Z)-endoxifen significantly reduced MBD to a degree comparable to the established 20 mg dose of tamoxifen. The 1 mg dosage of (Z)-endoxifen indicated superior tolerability. Future studies are necessary to confirm impact on breast cancer incidence.","publication_date":"2026-05-04T00:00:00"},"crossref":{"DOI":"10.1093/jnci/djag087","URL":"https://doi.org/10.1093/jnci/djag087","ISSN":["0027-8874","1460-2105"],"link":[{"URL":"https://academic.oup.com/jnci/advance-article-pdf/doi/10.1093/jnci/djag087/68192919/djag087.pdf","content-type":"application/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https://academic.oup.com/jnci/advance-article-pdf/doi/10.1093/jnci/djag087/68192919/djag087.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Endoxifen for mammographic density reduction—results from the KARISMA endoxifen trial"],"author":[{"given":"Per","family":"Hall","sequence":"first","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm,"},{"name":"Department of Oncology, Södersjukhuset , Stockholm,"}]},{"given":"Mattias","family":"Hammarström","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm,"}]},{"given":"Jenny","family":"Bergqvist","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm,"},{"name":"Department of Oncology, St Görans sjukhus , Stockholm,"}]},{"given":"Kamila","family":"Czene","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm,"}]},{"given":"Mikael","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm,"}]},{"given":"Marike","family":"Gabrielson","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm,"}]},{"given":"José","family":"Tapia","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm,"}]},{"given":"Steven","family":"Quay","sequence":"additional","affiliation":[{"name":"Atossa Therapeutics , Seattle, WA,"}]},{"given":"Stephen","family":"Nash","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm,"}]},{"given":"Magnus","family":"Bäcklund","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm,"}]}],"funder":[{"name":"Atossa Therapeutics"},{"id":[{"id":"10.13039/501100004047","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100004047","name":"Karolinska 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Density","value_numeric":null},{"paper_doi":"10.1093/jnci/djag087","tag_type":"generic","value":"endoxifen","value_numeric":null},{"paper_doi":"10.1093/jnci/djag087","tag_type":"generic","value":"tamoxifen","value_numeric":null},{"paper_doi":"10.1093/jnci/djag087","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1093/jnci/djag087","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1093/jnci/djag087","tag_type":"modality","value":"Selective Estrogen Receptor Modulator","value_numeric":null},{"paper_doi":"10.1093/jnci/djag087","tag_type":"sample_size","value":"n=240","value_numeric":240},{"paper_doi":"10.1093/jnci/djag087","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1093/jnci/djag087","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1093/jnci/djag087","tag_type":"warning","value":"MBD is used as a surrogate endpoint; no breast cancer incidence data are reported, so clinical impact_flag of 'practice_changing' reflects density reduction efficacy only — not confirmed cancer prevention benefit.","value_numeric":null},{"paper_doi":"10.1093/jnci/djag087","tag_type":"warning","value":"No direct head-to-head comparison with tamoxifen 20 mg was included in this trial; comparability to tamoxifen is inferred from historical benchmarks.","value_numeric":null},{"paper_doi":"10.1093/jnci/djag087","tag_type":"warning","value":"Trial was conducted in a single country (Sweden) among women in a national screening program, which may limit generalizability to other populations.","value_numeric":null}],"summaries":{"what_studied":"Double-blind RCT in 240 healthy premenopausal women comparing daily (Z)-endoxifen (1 mg or 2 mg) vs. placebo over 6 months, measuring mammographic breast density (MBD) change, safety, and tolerability.","key_result":"Both doses significantly reduced MBD vs. placebo: −19.3% (95% CI −6.15% to −32.4%) with 1 mg and −26.5% (95% CI −14.1% to −38.9%) with 2 mg — comparable to tamoxifen 20 mg. Discontinuations due to adverse events: 4 (placebo), 5 (1 mg), 11 (2 mg); 2 mg arm had significantly more vasomotor symptoms.","limitations":"MBD is a surrogate endpoint; direct impact on breast cancer incidence is unconfirmed. Trial enrolled only healthy premenopausal women from a single national screening program, limiting generalizability. No active tamoxifen comparator arm was included.","practice_takeaway":"Low-dose (Z)-endoxifen (1 mg/day) reduces mammographic density comparably to standard tamoxifen 20 mg with better tolerability — making it a promising chemoprevention candidate. Clinicians should await breast cancer incidence data before adopting it in practice."}},{"doi":"10.1161/circresaha.125.327297","pmid":"41834725","title":"RHOT Proteins Link Mitochondrial Motility to Cardiomyocyte Sarcomere Maturation","journal_title":"Circulation Research","journal_issn":"0009-7330","published_at":"2026-03-16T00:00:00.000Z","url":"https://doi.org/10.1161/circresaha.125.327297","source_score":19,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-09T13:22:38.136Z","updated_at":"2026-05-09T13:22:38.136Z","tags":[{"paper_doi":"10.1161/circresaha.125.327297","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.327297","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.327297","tag_type":"condition","value":"Cardiomyopathy","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.327297","tag_type":"condition","value":"Heart Failure","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.327297","tag_type":"condition","value":"Sarcomere Disarray","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.327297","tag_type":"generic","value":"tamoxifen","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.327297","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.327297","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.327297","tag_type":"modality","value":"Genetic Knockout Model","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.327297","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.327297","tag_type":"study_design","value":"Animal Experimental Study","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.327297","tag_type":"warning","value":"Sample sizes for individual experiments are not reported in the abstract or results summary; exact n values are in supplemental materials.","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.327297","tag_type":"warning","value":"The 'practice_changing' impact flag reflects mechanistic novelty in basic science, not a change in clinical treatment guidelines.","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.327297","tag_type":"warning","value":"The study used predominantly male mice for most adult time points; female data were collected but not the primary analysis.","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.327297","tag_type":"warning","value":"This is a preclinical mouse study; direct clinical translation to human cardiomyopathy is not established.","value_numeric":null}],"summaries":{"what_studied":"This study tested whether RHOT1/2 proteins — outer mitochondrial membrane GTPases that link mitochondria to motor proteins — are required for mitochondrial positioning during cardiomyocyte development. Two mouse models were compared: embryonic cardiomyocyte-selective Rhot1/2 knockout (cRhot1/2-KO) and tamoxifen-inducible adult knockout (iRhot1/2-KO).","key_result":"Embryonic deletion of Rhot1/2 caused fatal cardiomyopathy with sarcomere disarray and perinuclear mitochondrial/ATP accumulation, despite preserved mitochondrial respiratory capacity. Adult inducible deletion impaired isolated mitochondria motility but left sarcomere structure, intracellular mitochondrial distribution, local ATP production, and cardiac function intact — the majority of cRhot1/2-KO mice died after 28 weeks.","limitations":"- Cre was driven by αMHC (Myh6), active from embryonic day 9.5, so the earliest developmental window of Rhot deletion could not be isolated; distinct early-embryonic targeting strategies were not tested.\n- Male mice were the primary focus for most time points; sex-specific differences were noted but not fully explored.\n- FRET-based ATP measurements required 48-hour adenoviral infection of isolated cardiomyocytes, which may itself alter bioenergetics.","practice_takeaway":"RHOT-mediated mitochondrial motility is critical only during cardiac development, not in the mature heart — this finding points to the developmental window as the relevant therapeutic target if RHOT dysfunction contributes to congenital or pediatric cardiomyopathy. Clinicians should be aware that mitochondrial respiratory capacity can be preserved even when mitochondrial positioning — and local ATP delivery to sarcomeres — is severely disrupted."}}],"initialOffset":8,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"generic","value":"tamoxifen"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Generics","href":"/hub/tag/generic"},{"name":"tamoxifen"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"generic","hub_tag_value":"tamoxifen"}}}]]

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