{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T06:49:56Z","timestamp":1769237396812,"version":"3.49.0"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":40,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan","award":["23K24589"],"award-info":[{"award-number":["23K24589"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-32037-3","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T22:35:53Z","timestamp":1765406153000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oxidative DNA damage induced by 3,4-diOH-TAM, a tamoxifen metabolite, in relation to endometrial carcinogenesis"],"prefix":"10.1038","volume":"16","author":[{"given":"Yurie","family":"Mori","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaoru","family":"Midorikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Oikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyoshi","family":"Fukuhara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shosuke","family":"Kawanishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariko","family":"Murata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"32037_CR1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s12672-021-00411-y","volume":"12","author":"NS Ahmed","year":"2021","unstructured":"Ahmed, N. S., Samec, M., Liskova, A., Kubatka, P. & Saso, L. Tamoxifen and oxidative stress: an overlooked connection. Discov Oncol. 12, 17. https:\/\/doi.org\/10.1007\/s12672-021-00411-y (2021).","journal-title":"Discov Oncol."},{"key":"32037_CR2","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1093\/jnci\/djp018","volume":"101","author":"SR Cummings","year":"2009","unstructured":"Cummings, S. R. et al. Prevention of breast cancer in postmenopausal women: approaches to estimating and reducing risk. J. Natl. Cancer Inst. 101, 384\u2013398 (2009).","journal-title":"J. Natl. Cancer Inst."},{"key":"32037_CR3","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/S0140-6736(03)12342-2","volume":"361","author":"J Cuzick","year":"2003","unstructured":"Cuzick, J. et al. Overview of the main outcomes in breast-cancer prevention trials. Lancet 361, 296\u2013300 (2003).","journal-title":"Lancet"},{"key":"32037_CR4","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/s41416-023-02293-z","volume":"129","author":"M Hammarstrom","year":"2023","unstructured":"Hammarstrom, M. et al. Side effects of low-dose tamoxifen: results from a six-armed randomised controlled trial in healthy women. Br. J. Cancer. 129, 61\u201371. https:\/\/doi.org\/10.1038\/s41416-023-02293-z (2023).","journal-title":"Br. J. Cancer"},{"key":"32037_CR5","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1186\/s12885-023-11242-1","volume":"23","author":"F Gernier","year":"2023","unstructured":"Gernier, F. et al. Impact of web application support versus standard management on adherence with adjuvant hormone therapy in patients treated for breast cancer: the WEBAPPAC study. BMC Cancer. 23, 736. https:\/\/doi.org\/10.1186\/s12885-023-11242-1 (2023).","journal-title":"BMC Cancer"},{"key":"32037_CR6","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1124\/jpet.104.065607","volume":"310","author":"Z Desta","year":"2004","unstructured":"Desta, Z., Ward, B. A., Soukhova, N. V. & Flockhart, D. A. Comprehensive evaluation of Tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J. Pharmacol. Exp. Ther. 310, 1062\u20131075 (2004).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"32037_CR7","first-page":"1283","volume":"56","author":"SS Dehal","year":"1996","unstructured":"Dehal, S. S. & Kupfer, D. Evidence that the catechol 3,4-dihydroxytamoxifen is a proximate intermediate to the reactive species binding covalently to proteins. Cancer Res. 56, 1283\u20131290 (1996).","journal-title":"Cancer Res."},{"key":"32037_CR8","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1021\/tx990145n","volume":"13","author":"F Zhang","year":"2000","unstructured":"Zhang, F. et al. Synthesis and reactivity of a potential carcinogenic metabolite of tamoxifen: 3,4-dihydroxytamoxifen-o-quinone. Chem. Res. Toxicol. 13, 53\u201362 (2000).","journal-title":"Chem. Res. Toxicol."},{"key":"32037_CR9","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1007\/s00204-007-0188-3","volume":"81","author":"K Wozniak","year":"2007","unstructured":"Wozniak, K. et al. The DNA-damaging potential of tamoxifen in breast cancer and normal cells. Arch. Toxicol. 81, 519\u2013527 (2007).","journal-title":"Arch. Toxicol."},{"key":"32037_CR10","doi-asserted-by":"publisher","first-page":"2112","DOI":"10.1038\/s41598-025-86586-8","volume":"15","author":"A Nakamura","year":"2025","unstructured":"Nakamura, A. et al. Rapamycin inhibits tamoxifen-induced endometrial proliferation in vitro as a pilot approach for endometrial protection in breast cancer. Sci. Rep. 15, 2112. https:\/\/doi.org\/10.1038\/s41598-025-86586-8 (2025).","journal-title":"Sci. Rep."},{"key":"32037_CR11","doi-asserted-by":"publisher","DOI":"10.1007\/s12282-025-01769-5","author":"C Kawamura","year":"2025","unstructured":"Kawamura, C. et al. Risk of endometrial cancer among breast cancer survivors in Japan: a matched cohort study. Breast Cancer. https:\/\/doi.org\/10.1007\/s12282-025-01769-5 (2025).","journal-title":"Breast Cancer"},{"key":"32037_CR12","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1158\/1940-6207.CAPR-19-0424","volume":"13","author":"RJ Thorneloe","year":"2020","unstructured":"Thorneloe, R. J. et al. Knowledge of potential harms and benefits of tamoxifen among women considering breast cancer preventive therapy. Cancer Prev. Res. (Phila). 13, 411\u2013422. https:\/\/doi.org\/10.1158\/1940-6207.CAPR-19-0424 (2020).","journal-title":"Cancer Prev. Res. (Phila)"},{"key":"32037_CR13","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1289\/ehp.104-1469411","volume":"104","author":"IARC-Working-Group","year":"1996","unstructured":"IARC-Working-Group. IARC on tamoxifen. Environ. Health Perspect. 104, 688 (1996).","journal-title":"Environ. Health Perspect."},{"key":"32037_CR14","doi-asserted-by":"publisher","unstructured":"Emons, G., Mustea, A. & Tempfer, C. Tamoxifen and endometrial cancer: A janus-headed drug. Cancers (Basel) 12. https:\/\/doi.org\/10.3390\/cancers12092535 (2020).","DOI":"10.3390\/cancers12092535"},{"key":"32037_CR15","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1093\/carcin\/21.8.1461","volume":"21","author":"S Shibutani","year":"2000","unstructured":"Shibutani, S. et al. Identification of tamoxifen-DNA adducts in the endometrium of women treated with tamoxifen. Carcinogenesis 21, 1461\u20131467 (2000).","journal-title":"Carcinogenesis"},{"key":"32037_CR16","first-page":"8461","volume":"63","author":"EA Martin","year":"2003","unstructured":"Martin, E. A. et al. Tamoxifen DNA damage detected in human endometrium using accelerator mass spectrometry. Cancer Res. 63, 8461\u20138465 (2003).","journal-title":"Cancer Res."},{"key":"32037_CR17","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1093\/carcin\/bgu029","volume":"35","author":"EE Hernandez-Ramon","year":"2014","unstructured":"Hernandez-Ramon, E. E. et al. Tamoxifen-DNA adduct formation in monkey and human reproductive organs. Carcinogenesis 35, 1172\u20131176. https:\/\/doi.org\/10.1093\/carcin\/bgu029 (2014).","journal-title":"Carcinogenesis"},{"key":"32037_CR18","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.3892\/ol.2015.2962","volume":"9","author":"R Hu","year":"2015","unstructured":"Hu, R., Hilakivi-Clarke, L. & Clarke, R. Molecular mechanisms of tamoxifen-associated endometrial cancer (review). Oncol. Lett. 9, 1495\u20131501. https:\/\/doi.org\/10.3892\/ol.2015.2962 (2015).","journal-title":"Oncol. Lett."},{"key":"32037_CR19","doi-asserted-by":"publisher","first-page":"503420","DOI":"10.1016\/j.mrgentox.2021.503420","volume":"873","author":"Y Mori","year":"2022","unstructured":"Mori, Y. et al. Mechanism of reactive oxygen species generation and oxidative DNA damage induced by acrylohydroxamic acid, a putative metabolite of acrylamide. Mutat. Res. Genet. Toxicol. Environ. Mutagen. 873, 503420. https:\/\/doi.org\/10.1016\/j.mrgentox.2021.503420 (2022).","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"key":"32037_CR20","first-page":"38","volume":"145","author":"PI Chumakov","year":"1990","unstructured":"Chumakov, P. I., Tatarkin, A. P. & Putilin, V. A. Gigantic pheochromocytoma of the left adrenal gland. Vestn Khir Im I I Grek. 145, 38 (1990).","journal-title":"Vestn Khir Im I I Grek"},{"key":"32037_CR21","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1074\/jbc.275.3.2003","volume":"275","author":"M Murata","year":"2000","unstructured":"Murata, M. & Kawanishi, S. Oxidative DNA damage by vitamin A and its derivative via superoxide generation. J. Biol. Chem. 275, 2003\u20132008 (2000).","journal-title":"J. Biol. Chem."},{"key":"32037_CR22","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/302033a0","volume":"302","author":"DJ Capon","year":"1983","unstructured":"Capon, D. J., Chen, E. Y., Levinson, A. D., Seeburg, P. H. & Goeddel, D. V. Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue. Nature 302, 33\u201337 (1983).","journal-title":"Nature"},{"key":"32037_CR23","doi-asserted-by":"publisher","first-page":"15435","DOI":"10.1016\/S0021-9258(19)84847-0","volume":"264","author":"K Yamamoto","year":"1989","unstructured":"Yamamoto, K. & Kawanishi, S. Hydroxyl free radical is not the main active species in site-specific DNA damage induced by copper (II) ion and hydrogen peroxide. J. Biol. Chem. 264, 15435\u201315440 (1989).","journal-title":"J. Biol. Chem."},{"key":"32037_CR24","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1080\/10715762.2018.1562179","volume":"53","author":"Y Mori","year":"2019","unstructured":"Mori, Y. et al. Mechanisms of DNA damage induced by morin, an inhibitor of amyloid beta-peptide aggregation. Free Radic Res. 53, 115\u2013123. https:\/\/doi.org\/10.1080\/10715762.2018.1562179 (2019).","journal-title":"Free Radic Res."},{"key":"32037_CR25","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/S0076-6879(80)65059-9","volume":"65","author":"AM Maxam","year":"1980","unstructured":"Maxam, A. M. & Gilbert, W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 65, 499\u2013560 (1980).","journal-title":"Methods Enzymol."},{"key":"32037_CR26","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1093\/infdis\/jiac477","volume":"227","author":"H Kobayashi","year":"2023","unstructured":"Kobayashi, H. et al. Oxidative DNA damage by N4-hydroxycytidine, a metabolite of the SARS-CoV-2 antiviral molnupiravir. J. Infect. Dis. 227, 1068\u20131072. https:\/\/doi.org\/10.1093\/infdis\/jiac477 (2023).","journal-title":"J. Infect. Dis."},{"key":"32037_CR27","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/s0014-5793(03)01129-3","volume":"554","author":"M Murata","year":"2003","unstructured":"Murata, M., Mizutani, M., Oikawa, S., Hiraku, Y. & Kawanishi, S. Oxidative DNA damage by hyperglycemia-related aldehydes and its marked enhancement by hydrogen peroxide. FEBS Lett. 554, 138\u2013142. https:\/\/doi.org\/10.1016\/s0014-5793(03)01129-3 (2003).","journal-title":"FEBS Lett."},{"key":"32037_CR28","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1038\/bjc.1996.179","volume":"73","author":"A Hartmann","year":"1996","unstructured":"Hartmann, A. et al. High frequency of p53 gene mutations in primary breast cancers in Japanese women, a low-incidence population. Br. J. Cancer. 73, 896\u2013901 (1996).","journal-title":"Br. J. Cancer"},{"key":"32037_CR29","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/351453a0","volume":"351","author":"AJ Levine","year":"1991","unstructured":"Levine, A. J., Momand, J. & Finlay, C. A. The p53 tumour suppressor gene. Nature 351, 453\u2013456 (1991).","journal-title":"Nature"},{"key":"32037_CR30","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1038\/35002510","volume":"403","author":"SD Bruner","year":"2000","unstructured":"Bruner, S. D., Norman, D. P. & Verdine, G. L. Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. Nature 403, 859\u2013866. https:\/\/doi.org\/10.1038\/35002510 (2000).","journal-title":"Nature"},{"key":"32037_CR31","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1038\/349431a0","volume":"349","author":"S Shibutani","year":"1991","unstructured":"Shibutani, S., Takeshita, M. & Grollman, A. P. Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG. Nature 349, 431\u2013434. https:\/\/doi.org\/10.1038\/349431a0 (1991).","journal-title":"Nature"},{"key":"32037_CR32","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/S0165-4608(02)00673-8","volume":"141","author":"K Isaka","year":"2003","unstructured":"Isaka, K. et al. Establishment of a new human cell line (EN) with TP53 mutation derived from endometrial carcinoma. Cancer Genet. Cytogenet. 141, 20\u201325 (2003).","journal-title":"Cancer Genet. Cytogenet."},{"key":"32037_CR33","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1002\/chem.200305311","volume":"10","author":"M Lucarini","year":"2004","unstructured":"Lucarini, M., Pedulli, G. F. & Guerra, M. A critical evaluation of the factors determining the effect of intramolecular hydrogen bonding on the O-H bond dissociation enthalpy of catechol and of flavonoid antioxidants. Chemistry 10, 933\u2013939. https:\/\/doi.org\/10.1002\/chem.200305311 (2004).","journal-title":"Chemistry"},{"key":"32037_CR34","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1021\/tx0503045","volume":"19","author":"A Umemoto","year":"2006","unstructured":"Umemoto, A. et al. Absence of DNA adduct in the leukocytes from breast cancer patients treated with toremifene. Chem. Res. Toxicol. 19, 421\u2013425. https:\/\/doi.org\/10.1021\/tx0503045 (2006).","journal-title":"Chem. Res. Toxicol."},{"key":"32037_CR35","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/0006-291X(78)91562-0","volume":"81","author":"WA Pryor","year":"1978","unstructured":"Pryor, W. A. & Tang, R. H. Ethylene formation from methional. Biochem. Biophys. Res. Commun. 81, 498\u2013503 (1978). doi:0006-291X(78)91562-0 [pii].","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"32037_CR36","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/0014-5793(81)80180-9","volume":"129","author":"RJ Youngman","year":"1981","unstructured":"Youngman, R. J. & Elstner, E. F. Oxygen species in paraquat toxicity: the crypto-OH radical. FEBS Lett. 129, 265\u2013268 (1981).","journal-title":"FEBS Lett."},{"key":"32037_CR37","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/s0891-5849(02)00779-7","volume":"32","author":"S Kawanishi","year":"2002","unstructured":"Kawanishi, S., Hiraku, Y., Murata, M. & Oikawa, S. The role of metals in site-specific DNA damage with reference to carcinogenesis. Free Radic Biol. Med. 32, 822\u2013832. https:\/\/doi.org\/10.1016\/s0891-5849(02)00779-7 (2002).","journal-title":"Free Radic Biol. Med."},{"key":"32037_CR38","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.2741\/3739","volume":"16","author":"M Murata","year":"2011","unstructured":"Murata, M. & Kawanishi, S. Mechanisms of oxidative DNA damage induced by carcinogenic arylamines. Front. Biosci. (Landmark Ed). 16, 1132\u20131143. https:\/\/doi.org\/10.2741\/3739 (2011).","journal-title":"Front. Biosci. (Landmark Ed)"},{"key":"32037_CR39","doi-asserted-by":"publisher","unstructured":"Barceloux, D. G. Copper. J. Toxicol. Clin. Toxicol. 37, 217\u2013230. https:\/\/doi.org\/10.1081\/clt-100102421 (1999).","DOI":"10.1081\/clt-100102421"},{"key":"32037_CR40","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/0041-008x(91)90048-j","volume":"110","author":"JL Sagripanti","year":"1991","unstructured":"Sagripanti, J. L., Goering, P. L. & Lamanna, A. Interaction of copper with DNA and antagonism by other metals. Toxicol. Appl. Pharmacol. 110, 477\u2013485. https:\/\/doi.org\/10.1016\/0041-008x(91)90048-j (1991).","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"32037_CR41","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.jphotobiol.2008.12.010","volume":"95","author":"Q Yu","year":"2009","unstructured":"Yu, Q. & Heikal, A. A. Two-photon autofluorescence dynamics imaging reveals sensitivity of intracellular NADH concentration and conformation to cell physiology at the single-cell level. J. Photochem. Photobiol B. 95, 46\u201357. https:\/\/doi.org\/10.1016\/j.jphotobiol.2008.12.010 (2009).","journal-title":"J. Photochem. Photobiol B"},{"key":"32037_CR42","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1021\/tx990144v","volume":"13","author":"PW Fan","year":"2000","unstructured":"Fan, P. W., Zhang, F. & Bolton, J. L. 4-Hydroxylated metabolites of the antiestrogens tamoxifen and toremifene are metabolized to unusually stable quinone methides. Chem. Res. Toxicol. 13, 45\u201352. https:\/\/doi.org\/10.1021\/tx990144v (2000).","journal-title":"Chem. Res. Toxicol."},{"key":"32037_CR43","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1021\/tx030004s","volume":"16","author":"X Liu","year":"2003","unstructured":"Liu, X. et al. Antiestrogenic and DNA damaging effects induced by tamoxifen and toremifene metabolites. Chem. Res. Toxicol. 16, 832\u2013837. https:\/\/doi.org\/10.1021\/tx030004s (2003).","journal-title":"Chem. Res. Toxicol."},{"key":"32037_CR44","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.ccell.2020.06.001","volume":"38","author":"JD Hayes","year":"2020","unstructured":"Hayes, J. D., Dinkova-Kostova, A. T. & Tew, K. D. Oxidative stress in cancer. Cancer Cell. 38, 167\u2013197. https:\/\/doi.org\/10.1016\/j.ccell.2020.06.001 (2020).","journal-title":"Cancer Cell."},{"key":"32037_CR45","doi-asserted-by":"publisher","first-page":"5191","DOI":"10.1038\/onc.2012.638","volume":"32","author":"O Nagano","year":"2013","unstructured":"Nagano, O., Okazaki, S. & Saya, H. Redox regulation in stem-like cancer cells by CD44 variant isoforms. Oncogene 32, 5191\u20135198. https:\/\/doi.org\/10.1038\/onc.2012.638 (2013).","journal-title":"Oncogene"},{"key":"32037_CR46","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1021\/bi035613d","volume":"43","author":"M Murata","year":"2004","unstructured":"Murata, M., Midorikawa, K., Koh, M., Umezawa, K. & Kawanishi, S. Genistein and Daidzein induce cell proliferation and their metabolites cause oxidative DNA damage in relation to isoflavone-induced cancer of estrogen-sensitive organs. Biochemistry 43, 2569\u20132577 (2004).","journal-title":"Biochemistry"},{"key":"32037_CR47","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1017\/S0029665118002884","volume":"78","author":"Y Dunneram","year":"2019","unstructured":"Dunneram, Y., Greenwood, D. C. & Cade, J. E. Diet, menopause and the risk of ovarian, endometrial and breast cancer. Proc. Nutr. Soc. 78, 438\u2013448. https:\/\/doi.org\/10.1017\/S0029665118002884 (2019).","journal-title":"Proc. Nutr. Soc."},{"key":"32037_CR48","doi-asserted-by":"publisher","first-page":"2035","DOI":"10.1007\/s00432-021-03629-z","volume":"147","author":"D Huber","year":"2021","unstructured":"Huber, D., Seitz, S., Kast, K., Emons, G. & Ortmann, O. Hormone replacement therapy in BRCA mutation carriers and risk of ovarian, endometrial, and breast cancer: a systematic review. J. Cancer Res. Clin. Oncol. 147, 2035\u20132045. https:\/\/doi.org\/10.1007\/s00432-021-03629-z (2021).","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"32037_CR49","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.pharmthera.2013.05.005","volume":"139","author":"G Yang","year":"2013","unstructured":"Yang, G., Nowsheen, S., Aziz, K. & Georgakilas, A. G. Toxicity and adverse effects of tamoxifen and other anti-estrogen drugs. Pharmacol. Ther. 139, 392\u2013404. https:\/\/doi.org\/10.1016\/j.pharmthera.2013.05.005 (2013).","journal-title":"Pharmacol. Ther."},{"key":"32037_CR50","doi-asserted-by":"publisher","first-page":"1890","DOI":"10.7150\/thno.19135","volume":"7","author":"L Feng","year":"2017","unstructured":"Feng, L. et al. Tamoxifen activates Nrf2-dependent SQSTM1 transcription to promote endometrial hyperplasia. Theranostics 7, 1890\u20131900. https:\/\/doi.org\/10.7150\/thno.19135 (2017).","journal-title":"Theranostics"},{"key":"32037_CR51","doi-asserted-by":"publisher","first-page":"2192","DOI":"10.1038\/s41588-025-02308-w","volume":"57","author":"K Kubler","year":"2025","unstructured":"Kubler, K. et al. Tamoxifen induces PI3K activation in uterine cancer. Nat. Genet. 57, 2192\u20132202. https:\/\/doi.org\/10.1038\/s41588-025-02308-w (2025).","journal-title":"Nat. Genet."},{"key":"32037_CR52","doi-asserted-by":"publisher","unstructured":"Alves, C. L. & Ditzel, H. J. Drugging the PI3K\/AKT\/mTOR pathway in ER\u2009+\u2009breast cancer. Int. J. Mol. Sci. 24 https:\/\/doi.org\/10.3390\/ijms24054522 (2023).","DOI":"10.3390\/ijms24054522"},{"key":"32037_CR53","doi-asserted-by":"publisher","first-page":"827724","DOI":"10.3389\/fendo.2022.827724","volume":"13","author":"K Yu","year":"2022","unstructured":"Yu, K. et al. Estrogen receptor function: impact on the human endometrium. Front. Endocrinol. (Lausanne). 13, 827724. https:\/\/doi.org\/10.3389\/fendo.2022.827724 (2022).","journal-title":"Front. Endocrinol. (Lausanne)"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-32037-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-32037-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-32037-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T01:07:05Z","timestamp":1769216825000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-32037-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,10]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["32037"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-32037-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,10]]},"assertion":[{"value":"23 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2351"}}