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Twenty-Year Benefit...
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Johansson, AnnelieKarolinska Institutet
(author)
Twenty-Year Benefit From Adjuvant Goserelin and Tamoxifen in Premenopausal Patients With Breast Cancer in a Controlled Randomized Clinical Trial
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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Lippincott, Williams & Wilkins,2022
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:liu-190792
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-190792URI
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https://doi.org/10.1200/JCO.21.02844DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:151385502URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Funding Agencies|Swedish Research Council (Vetenskapsradet); Swedish Research Council for Health, Working life and Welfare (FORTE) [2020-02466]; ALF medicine [2019-00477]; GostaMilton Donation Fund (Stiftelsen Gosta Miltons donationsfond ) [LS2018-1157]; Swedish Cancer Society (Cancerfonden); Stockholm Cancer Society (Cancerforeningen i Stockholm) [190268, 200802, 190140]; California Breast Cancer Research Program (CBCRP) [181093, 204152, 201212]; National Institutes of Health (NIH) [180B-0065]; Horizon 2020 [U01-CA196406]; [672570]
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PURPOSETo assess the long-term (20-year) endocrine therapy benefit in premenopausal patients with breast cancer.METHODSSecondary analysis of the Stockholm trial (STO-5, 1990-1997) randomly assigning 924 premenopausal patients to 2 years of goserelin (3.6 mg subcutaneously once every 28 days), tamoxifen (40 mg orally once daily), combined goserelin and tamoxifen, or no adjuvant endocrine therapy (control) is performed. Random assignment was stratified by lymph node status; lymph node-positive patients (n = 459) were allocated to standard chemotherapy (cyclophosphamide, methotrexate, and fluorouracil). Primary tumor immunohistochemistry (n = 731) and gene expression profiling (n = 586) were conducted in 2020. The 70-gene signature identified genomic low-risk and high-risk patients. Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and multivariable time-varying flexible parametric modeling assessed the long-term distant recurrence-free interval (DRFI). Swedish high-quality registries allowed a complete follow-up of 20 years.RESULTSIn estrogen receptor-positive patients (n = 584, median age 47 years), goserelin, tamoxifen, and the combination significantly improved long-term distant recurrence-free interval compared with control (multivariable hazard ratio [HR], 0.49; 95% CI, 0.32 to 0.75, HR, 0.57; 95% CI, 0.38 to 0.87, and HR, 0.63; 95% CI, 0.42 to 0.94, respectively). Significant goserelin-tamoxifen interaction was observed (P = .016). Genomic low-risk patients (n = 305) significantly benefitted from tamoxifen (HR, 0.24; 95% CI, 0.10 to 0.60), and genomic high-risk patients (n = 158) from goserelin (HR, 0.24; 95% CI, 0.10 to 0.54). Increased risk from the addition of tamoxifen to goserelin was seen in genomic high-risk patients (HR, 3.36; 95% CI, 1.39 to 8.07). Moreover, long-lasting 20-year tamoxifen benefit was seen in genomic low-risk patients, whereas genomic high-risk patients had early goserelin benefit.CONCLUSIONThis study shows 20-year benefit from 2 years of adjuvant endocrine therapy in estrogen receptor-positive premenopausal patients and suggests differential treatment benefit on the basis of tumor genomic characteristics. Combined goserelin and tamoxifen therapy showed no benefit over single treatment. Long-term follow-up to assess treatment benefit is critical.
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Dar, HumaKarolinska Institutet
(author)
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Veer, Laura J. van tUniv Calif San Francisco, CA USA
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Tobin, Nicholas P.Karolinska Institutet
(author)
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Perez-Tenorio, GizehLinköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US(Swepub:liu)gizpe86
(author)
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Nordenskjöld, AnnaGothenburg Univ, Sweden
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Johansson, UllaKarolinska Univ Hosp, Sweden
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Hartman, JohanKarolinska Institutet
(author)
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Skoog, LambertKarolinska Institutet
(author)
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Yau, ChristinaBuck Inst Res Aging, CA USA; Univ Calif San Francisco, CA USA
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Benz, Christopher C.Buck Inst Res Aging, CA USA; Univ Calif San Francisco, CA USA
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Esserman, Laura J.Univ Calif San Francisco, CA USA
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Stål, OlleLinköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US(Swepub:liu)ollst87
(author)
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Nordenskjöld, BoLinköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US(Swepub:liu)bono64
(author)
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Fornander, TommyKarolinska Inst, Sweden
(author)
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Lindstrom, Linda S.Karolinska Inst, Sweden
(author)
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Karolinska InstitutetUniv Calif San Francisco, CA USA
(creator_code:org_t)
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In:Journal of Clinical Oncology: Lippincott, Williams & Wilkins40:35, s. 4071-40820732-183X1527-7755
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