Tamoxifen and Endometrial Cancer: A Janus-Headed Drug

被引：54

作者：

Emons, Gunter ^{[1
]}

Mustea, Alexander ^{[2
]}

Tempfer, Clemens ^{[3
]}

机构：

[1] Georg August Univ, Dept Obstet & Gynecol, D-37075 Gottingen, Germany

[2] Univ Hosp, Dept Gynecol & Gynecol Oncol, D-53127 Bonn, Germany

[3] Ruhr Univ, Dept Obstet & Gynecol, D-44625 Herne, Germany

来源：

CANCERS | 2020年 / 12卷 / 09期

关键词：

tamoxifen; endometrial cancer; selective estrogen receptor modulator; PATIENT-LEVEL METAANALYSIS; BREAST-CANCER; PHASE-II; AROMATASE INHIBITORS; ADJUVANT TAMOXIFEN; CARCINOMA; RISK; ESTROGEN; THERAPY; WOMEN;

D O I：

10.3390/cancers12092535

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary Tamoxifen, an antiestrogen, is a potent drug to treat and prevent hormone dependent breast cancer. As it has low toxicity and is widely available, tamoxifen has become one of the most frequently prescribed anticancer drugs worldwide. A major side effect of tamoxifen is to increase the risk of uterine corpus cancer (endometrial cancer). This happens after long-term (>2 years) application, especially in postmenopausal women with preexisting pathologies in the uterus. On the other hand, tamoxifen is an efficacious treatment for certain forms of advanced endometrial cancer, thus making it a Janus-headed drug that can support the development of endometrial cancer on one hand and be used as a remedy for this disease on the other. This article reviews the clinical data on these controversial effects of tamoxifen and the possible explanations. Tamoxifen is a selective estrogen receptor modulator used for the treatment and prevention of estrogen receptor (ER)-positive breast cancer. However, tamoxifen increases the risk of endometrial cancer (EC) by about 2-7 fold, and more aggressive types of EC with poor prognoses are observed in tamoxifen users. On the other hand, tamoxifen is an efficacious treatment for advanced or recurrent EC with low toxicity. The differential agonistic or antagonistic effects of tamoxifen on ER alpha are explained by the tissue-specific expression profiles of co-activators and co-repressors of the receptor. The estrogen-agonistic effect of tamoxifen in endometrial cancers can also be explained by the expression of G-protein coupled estrogen receptor 1 (GPER-1), a membrane-bound estrogen receptor for which tamoxifen and other "antiestrogens" are pure agonists.

引用

页码：1 / 11

页数：11

共 51 条

[1]

Abe O, 2005, LANCET, V366, P2087, DOI 10.1016/s0140-6736(05)66544-0

[2] Relationship between tamoxifen use and high risk endometrial cancer histologic types [J].

Bland, Amy E. ;

Calingaert, Brian ;

Secord, Angeles Alvarez ;

Lee, Paula S. ;

Valea, Fidel A. ;

Berchuck, Andrew ;

Soper, John T. ;

Havrilesky, Laura .

GYNECOLOGIC ONCOLOGY, 2009, 112 (01) :150-154

[3] Aromatase inhibitors, tamoxifen, and endometrial cancer in breast cancer survivors [J].

Chlebowski, Rowan T. ;

Schottinger, Joanne E. ;

Shi, Jiaxiao ;

Chung, Joanie ;

Haque, Reina .

CANCER, 2015, 121 (13) :2147-2155

[4] Risk of malignant mixed mullerian tumors after tamoxifen therapy for breast cancer [J].

Curtis, RE ;

Freedman, DM ;

Sherman, ME ;

Fraumeni, JF .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2004, 96 (01) :70-74

[5] Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials [J].

Davies, C. ;

Godwin, J. ;

Gray, R. ;

Clarke, M. ;

Darby, S. ;

McGale, P. ;

Wang, Y. C. ;

Peto, R. ;

Pan, H. C. ;

Cutter, D. ;

Taylor, C. ;

Ingle, J. .

LANCET, 2011, 378 (9793) :771-784

[6] Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial [J].

Davies, Christina ;

Pan, Hongchao ;

Godwin, Jon ;

Gray, Richard ;

Arriagada, Rodrigo ;

Raina, Vinod ;

Abraham, Mirta ;

Medeiros Alencar, Victor Hugo ;

Badran, Atef ;

Bonfill, Xavier ;

Bradbury, Joan ;

Clarke, Michael ;

Collins, Rory ;

Davis, Susan R. ;

Delmestri, Antonella ;

Forbes, John F. ;

Haddad, Peiman ;

Hou, Ming-Feng ;

Inbar, Moshe ;

Khaled, Hussein ;

Kielanowska, Joanna ;

Kwan, Wing-Hong ;

Mathew, Beela S. ;

Mittra, Indraneel ;

Mueller, Bettina ;

Nicolucci, Antonio ;

Peralta, Octavio ;

Pernas, Fany ;

Petruzelka, Lubos ;

Pienkowski, Tadeusz ;

Radhika, Ramachandran ;

Rajan, Balakrishnan ;

Rubach, Maryna T. ;

Tort, Sera ;

Urrutia, Gerard ;

Valentini, Miriam ;

Wang, Yaochen ;

Peto, Richard .

LANCET, 2013, 381 (9869) :805-816

[7] The benefits of adding metformin to tamoxifen to protect the endometrium-A randomized placebo-controlled trial [J].

Davis, Susan R. ;

Robinson, Penelope J. ;

Jane, Fiona ;

White, Shane ;

Brown, Kristy A. ;

Piessens, Sofie ;

Edwards, Andrew ;

McNeilage, Jane ;

Woinarski, Jillian ;

Chipman, Mitchell ;

Bell, Robin J. .

CLINICAL ENDOCRINOLOGY, 2018, 89 (05) :605-612

[8] Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen [J].

Dominick, Sally ;

Hickey, Martha ;

Chin, Jason ;

Su, H. Irene .

COCHRANE DATABASE OF SYSTEMATIC REVIEWS, 2015, (12)

[9] Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials [J].

Dowsett, M. ;

Forbes, J. F. ;

Bradley, R. ;

Ingle, J. ;

Aihara, T. ;

Bliss, J. ;

Boccardo, F. ;

Coates, A. ;

Coombes, R. C. ;

Cuzick, J. ;

Dubsky, P. ;

Gnant, M. ;

Kaufmann, M. ;

Kilburn, L. ;

Perrone, F. ;

Rea, D. ;

Thuerlimann, B. ;

van de Velde, C. ;

Pan, H. ;

Peto, R. ;

Davies, C. ;

Gray, R. ;

Baum, M. ;

Buzdar, A. ;

Sestak, I. ;

Markopoulos, C. ;

Fesl, C. ;

Jakesz, R. ;

Colleoni, M. ;

Gelber, R. ;

Regan, M. ;

von Minckwitz, G. ;

Snowdon, C. ;

Goss, P. ;

Pritchard, K. ;

Anderson, S. ;

Costantino, J. ;

Mamounas, E. ;

Ohashi, Y. ;

Watanabe, T. ;

Bastiaannet, E. .

LANCET, 2015, 386 (10001) :1341-1352

[10]

Earl H, 1997, Clin Oncol (R Coll Radiol), V9, P141, DOI 10.1016/S0936-6555(97)80067-2

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