2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.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\":\"Selective Estrogen Receptor Modulator: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Selective Estrogen Receptor Modulator (modality). Clinician-written summaries and actionable practice insights. 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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":"10.1200/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."}}],"initialOffset":4,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"Selective Estrogen Receptor Modulator"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"Selective Estrogen Receptor Modulator"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"Selective Estrogen Receptor Modulator"}}}]]

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