A randomized phase II presurgical trial of weekly low-dose tamoxifen versus raloxifene versus placebo in premenopausal women with estrogen receptor-positive breast cancer

Breast Cancer Research

Bernardo Bonanni⁴  Andrea DeCensi¹  Aliana Guerrieri-Gonzaga⁴  Clara Varricchio⁴  Massimiliano Cazzaniga⁴  Alberto Luini⁵  Fabricio Brenelli⁵  Fabio Bassi⁵  Maria Teresa Sandri⁶  Giancarlo Pruneri²  Irene Feroce⁴  Ernst Lien³  Jennifer Gjerde³  Harriet Johansson⁴  Debora Macis⁴  Sara Gandini⁷  Matteo Lazzeroni⁴  Davide Serrano⁴ 

[1] Division of Medical Oncology, E.O. Ospedali Galliera, Mura delle Cappuccine 14, Genova 16128, Italy;University of Milan School of Medicine, via Festa del Perdono 7, 20122 Milan, Italy;Hormone Laboratory, Haukeland University Hospital Institute of Medicine, University of Bergen, Jonas Lies vei 53, N-5021 Bergen, Norway;Division of Cancer Prevention and Genetics, European Institute of Oncology, via Ripamonti 435, Milan 20141 Italy;Division of Senology, European Institute of Oncology, via Ripamonti 435, Milan 20141, Italy;Unit of Laboratory Medicine, European Institute of Oncology, via Ripamonti 435, Milan 20141, Italy;Division of Epidemiology and Biostatistics, European Institute of Oncology, via Ripamonti 435, Milan 20141, Italy

关键词: prevention;    raloxifene;    tamoxifen;    breast cancer;   

Others  :  794528
DOI  :  10.1186/bcr3439

 received in 2012-08-20, accepted in 2013-06-20,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Serrano et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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