A randomized phase II pre-surgical trial of weekly low-dose tamoxifen versus raloxifene versus placebo in premenopausal women with estrogen receptor positive breast cancer
dc.contributor.author | Serrano, Davide | en_US |
dc.contributor.author | Lazzeroni, Matteo | en_US |
dc.contributor.author | Gandini, Sara | en_US |
dc.contributor.author | Macis, Debora | en_US |
dc.contributor.author | Johansson, Harriet | en_US |
dc.contributor.author | Gjerde, Jennifer | en_US |
dc.contributor.author | Lien, Ernst Asbjørn | en_US |
dc.contributor.author | Feroce, Irene | en_US |
dc.contributor.author | Pruneri, Giancarlo | en_US |
dc.contributor.author | Sandri, Maria Teresa | en_US |
dc.contributor.author | Bassi, Fabio | en_US |
dc.contributor.author | Brenelli, Fabricio | en_US |
dc.contributor.author | Luini, Alberto | en_US |
dc.contributor.author | Cazzaniga, Massimiliano | en_US |
dc.contributor.author | Varricchio, Clara | en_US |
dc.contributor.author | Guerrieri-Gonzaga, Aliana | en_US |
dc.contributor.author | DeCensi, Andrea | en_US |
dc.contributor.author | Bonanni, Bernardo | en_US |
dc.date.accessioned | 2014-09-18T14:00:16Z | |
dc.date.available | 2014-09-18T14:00:16Z | |
dc.date.issued | 2013-06-20 | eng |
dc.identifier.issn | 1465-5411 | |
dc.identifier.uri | https://hdl.handle.net/1956/8513 | |
dc.description.abstract | Introduction: We previously demonstrated that 1 or 5 mg per day of tamoxifen (T) given for four weeks before surgery reduces Ki-67 in breast cancer (BC) patients to the same extent as the standard 20 mg/d. Given the long half-life of T, a weekly dose (10 mg per week (w)) may be worth testing. Also, raloxifene (R) has shown Ki-67 reduction in postmenopausal patients in a preoperative setting, but data in premenopausal women are limited. We conducted a randomized trial testing T 10 mg/w vs. R 60 mg/d vs. placebo in a presurgical model. Methods: Out of 204 screened subjects, 57 were not eligible, 22 refused to participate and 125 were included in the study. The participants were all premenopausal women with estrogen receptor-positive BC. They were randomly assigned to either T 10mg/w or R 60 mg/d or placebo for six weeks before surgery. The primary endpoint was tissue change of Ki-67. Secondary endpoints were modulation of estrogen and progesterone receptors and several other circulating biomarkers. Results: Ki-67 was not significantly modulated by either treatment. In contrast, both selective estrogen receptor modulators (SERMs) significantly modulated circulating IGF-I/IGFBP-3 ratio, cholesterol, fibrinogen and antithrombin III. Estradiol was increased with both SERMs. Within the tamoxifen arm, CYP2D6 polymorphism analysis showed a higher concentration of N-desTamoxifen, one of the tamoxifen metabolites, in subjects with reduced CYP2D6 activity. Moreover, a reduction of Ki-67 and a marked increase of sex hormone-binding globulin (SHBG) were observed in the active phenotype. Conclusions: A weekly dose of tamoxifen and a standard dose of raloxifene did not inhibit tumor cell proliferation, measured as Ki-67 expression, in premenopausal BC patients. However, in the tamoxifen arm women with an extensive phenotype for CYP2D6 reached a significant Ki-67 modulation. | en_US |
dc.language.iso | eng | eng |
dc.publisher | BioMed Central | eng |
dc.rights | Attribution CC BY | eng |
dc.rights.uri | http://creativecommons.org/licenses/by/2.0 | eng |
dc.subject | Breast cancer | eng |
dc.subject | Tamoxifen | eng |
dc.subject | raloxifene | eng |
dc.subject | Prevention | eng |
dc.title | A randomized phase II pre-surgical trial of weekly low-dose tamoxifen versus raloxifene versus placebo in premenopausal women with estrogen receptor positive breast cancer | en_US |
dc.type | Peer reviewed | |
dc.type | Journal article | |
dc.date.updated | 2013-09-13T11:09:26Z | |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Davide Serrano et al.; licensee BioMed Central Ltd. | |
dc.rights.holder | Copyright 2013 Serrano et al.; licensee BioMed Central Ltd. | |
dc.source.articlenumber | R47 | |
dc.identifier.doi | https://doi.org/10.1186/bcr3439 | |
dc.identifier.cristin | 1115243 | |
dc.source.journal | Breast Cancer Research | |
dc.source.40 | 15 |