{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:46:02Z","timestamp":1787849162379,"version":"build-2784847793"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer Res Treat"],"published-print":{"date-parts":[[2025,6]]},"DOI":"10.1007\/s10549-025-07660-3","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T11:51:53Z","timestamp":1741607513000},"page":"441-447","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["PTEN inactivating mutations are associated with hormone receptor loss during breast cancer recurrence"],"prefix":"10.1007","volume":"211","author":[{"given":"Haiying","family":"Zhan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay Mariadas","family":"Antony","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiming","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janie","family":"Theriot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanxin","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Hui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uma","family":"Krishnamurti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"DiGiovanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,10]]},"reference":[{"key":"7660_CR1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dju055","author":"N Howlader","year":"2014","unstructured":"Howlader N et al (2014) US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. https:\/\/doi.org\/10.1093\/jnci\/dju055","journal-title":"J Natl Cancer Inst"},{"key":"7660_CR2","doi-asserted-by":"publisher","first-page":"1836","DOI":"10.1056\/NEJMoa1701830","volume":"377","author":"H Pan","year":"2017","unstructured":"Pan H et al (2017) 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med 377:1836\u20131846","journal-title":"N Engl J Med"},{"key":"7660_CR3","doi-asserted-by":"publisher","first-page":"2557","DOI":"10.1056\/NEJMra1307118","volume":"383","author":"HJ Burstein","year":"2020","unstructured":"Burstein HJ (2020) Systemic therapy for estrogen receptor-positive, HER2-negative breast cancer. N Engl J Med 383:2557\u20132570","journal-title":"N Engl J Med"},{"key":"7660_CR4","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1016\/S0140-6736(11)60993-8","volume":"378","author":"Early Breast Cancer Trialists\u2019 Collaborative Group","year":"2011","unstructured":"Early Breast Cancer Trialists\u2019 Collaborative Group et al (2011) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen. The Lancet 378:771\u2013784","journal-title":"The Lancet"},{"key":"7660_CR5","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1093\/jnci\/djx273","volume":"110","author":"W Schrijver","year":"2018","unstructured":"Schrijver W et al (2018) Receptor conversion in distant breast cancer metastases: a systematic review and meta-analysis. J Natl Cancer Inst 110:568\u2013580","journal-title":"J Natl Cancer Inst"},{"key":"7660_CR6","doi-asserted-by":"publisher","first-page":"2601","DOI":"10.1200\/JCO.2011.37.2482","volume":"30","author":"LS Lindstrom","year":"2012","unstructured":"Lindstrom LS et al (2012) Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. J Clin Oncol 30:2601\u20132608","journal-title":"J Clin Oncol"},{"key":"7660_CR7","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.ejca.2013.10.004","volume":"50","author":"G Aurilio","year":"2014","unstructured":"Aurilio G et al (2014) A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases. Eur J Cancer 50:277\u2013289","journal-title":"Eur J Cancer"},{"key":"7660_CR8","first-page":"277","volume":"17","author":"P Arapantoni-Dadioti","year":"2012","unstructured":"Arapantoni-Dadioti P et al (2012) Discordant expression of hormone receptors and HER2 in breast cancer. A retrospective comparison of primary tumors with paired metachronous recurrences or metastases. J BUON 17:277\u2013283","journal-title":"J BUON"},{"key":"7660_CR9","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-024-07431-6","author":"GP Dowling","year":"2024","unstructured":"Dowling GP et al (2024) Receptor Discordance in Metastatic Breast Cancer; a review of clinical and genetic subtype alterations from primary to metastatic disease. Breast Cancer Res Treat. https:\/\/doi.org\/10.1007\/s10549-024-07431-6","journal-title":"Breast Cancer Res Treat"},{"key":"7660_CR10","doi-asserted-by":"publisher","first-page":"2796","DOI":"10.1158\/2159-8290.CD-20-1647","volume":"11","author":"P Aftimos","year":"2021","unstructured":"Aftimos P et al (2021) Genomic and transcriptomic analyses of breast cancer primaries and matched metastases in AURORA, the Breast International Group (BIG) molecular screening initiative. Cancer Discov 11:2796\u20132811","journal-title":"Cancer Discov"},{"key":"7660_CR11","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1158\/0008-5472.CAN-16-2717","volume":"77","author":"JM Cejalvo","year":"2017","unstructured":"Cejalvo JM et al (2017) Intrinsic subtypes and gene expression profiles in primary and metastatic breast cancer. Cancer Res 77:2213\u20132221","journal-title":"Cancer Res"},{"key":"7660_CR12","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1093\/annonc\/mdu450","volume":"26","author":"R Salgado","year":"2015","unstructured":"Salgado R et al (2015) The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol 26:259\u2013271","journal-title":"Ann Oncol"},{"key":"7660_CR13","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1001\/jamaoncol.2016.0891","volume":"2","author":"SZ Millis","year":"2016","unstructured":"Millis SZ, Ikeda S, Reddy S, Gatalica Z, Kurzrock R (2016) Landscape of phosphatidylinositol-3-kinase pathway alterations across 19 784 diverse solid tumors. JAMA Oncol 2:1565\u20131573","journal-title":"JAMA Oncol"},{"key":"7660_CR14","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/nature11412","volume":"490","author":"Cancer Genome Atlas Network","year":"2012","unstructured":"Cancer Genome Atlas Network (2012) Comprehensive molecular portraits of human breast tumours. Nature 490:61\u201370","journal-title":"Nature"},{"key":"7660_CR15","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.1158\/2159-8290.CD-18-0264","volume":"8","author":"B O\u2019Leary","year":"2018","unstructured":"O\u2019Leary B et al (2018) The genetic landscape and clonal evolution of breast cancer resistance to palbociclib plus fulvestrant in the PALOMA-3 trial. Cancer Discov 8:1390\u20131403","journal-title":"Cancer Discov"},{"key":"7660_CR16","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1158\/2159-8290.CD-19-1390","volume":"10","author":"SA Wander","year":"2020","unstructured":"Wander SA et al (2020) The genomic landscape of intrinsic and acquired resistance to cyclin-dependent kinase 4\/6 inhibitors in patients with hormone receptor-positive metastatic breast cancer. Cancer Discov 10:1174\u20131193","journal-title":"Cancer Discov"},{"key":"7660_CR17","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1016\/j.annonc.2021.09.019","volume":"32","author":"A Gennari","year":"2021","unstructured":"Gennari A et al (2021) ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol 32:1475\u20131495","journal-title":"Ann Oncol"},{"key":"7660_CR18","doi-asserted-by":"publisher","first-page":"2357","DOI":"10.1093\/annonc\/mdu456","volume":"25","author":"M Piccart","year":"2014","unstructured":"Piccart M et al (2014) Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2dagger. Ann Oncol 25:2357\u20132362","journal-title":"Ann Oncol"},{"key":"7660_CR19","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1159\/000354121","volume":"8","author":"M Gnant","year":"2013","unstructured":"Gnant M, Greil R, Hubalek M, Steger G (2013) Everolimus in postmenopausal, hormone receptor-positive advanced breast cancer: summary and results of an austrian expert panel discussion. Breast Care (Basel) 8:293\u2013299","journal-title":"Breast Care (Basel)"},{"key":"7660_CR20","first-page":"3657","volume":"57","author":"E Rhei","year":"1997","unstructured":"Rhei E et al (1997) Mutation analysis of the putative tumor suppressor gene PTEN\/MMAC1 in primary breast carcinomas. Cancer Res 57:3657\u20133659","journal-title":"Cancer Res"},{"key":"7660_CR21","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1023\/A:1006142919428","volume":"55","author":"ST Chen","year":"1999","unstructured":"Chen ST et al (1999) Mutation analysis of the putative tumor suppression gene PTEN\/MMAC1 in sporadic breast cancer. Breast Cancer Res Treat 55:85\u201389","journal-title":"Breast Cancer Res Treat"},{"key":"7660_CR22","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1038\/sj.bjc.6690121","volume":"79","author":"D Freihoff","year":"1999","unstructured":"Freihoff D et al (1999) Exclusion of a major role for the PTEN tumour-suppressor gene in breast carcinomas. Br J Cancer 79:754\u2013758","journal-title":"Br J Cancer"},{"key":"7660_CR23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002201","volume":"13","author":"C Lefebvre","year":"2016","unstructured":"Lefebvre C et al (2016) Mutational profile of metastatic breast cancers: a retrospective analysis. PLoS Med 13:e1002201","journal-title":"PLoS Med"},{"key":"7660_CR24","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1159\/000086981","volume":"68","author":"S Tsutsui","year":"2005","unstructured":"Tsutsui S et al (2005) Reduced expression of PTEN protein and its prognostic implications in invasive ductal carcinoma of the breast. Oncology 68:398\u2013404","journal-title":"Oncology"},{"key":"7660_CR25","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1038\/modpathol.3800296","volume":"18","author":"N Shoman","year":"2005","unstructured":"Shoman N et al (2005) Reduced PTEN expression predicts relapse in patients with breast carcinoma treated by tamoxifen. Mod Pathol 18:250\u2013259","journal-title":"Mod Pathol"},{"key":"7660_CR26","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/s41523-021-00251-7","volume":"7","author":"LM Smyth","year":"2021","unstructured":"Smyth LM et al (2021) Selective AKT kinase inhibitor capivasertib in combination with fulvestrant in PTEN-mutant ER-positive metastatic breast cancer. npj Breast Cancer 7:44","journal-title":"npj Breast Cancer"},{"key":"7660_CR27","doi-asserted-by":"publisher","first-page":"9817","DOI":"10.1074\/jbc.M010840200","volume":"276","author":"RA Campbell","year":"2001","unstructured":"Campbell RA et al (2001) Phosphatidylinositol 3-kinase\/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance. J Biol Chem 276:9817\u20139824","journal-title":"J Biol Chem"},{"key":"7660_CR28","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1038\/nature13948","volume":"518","author":"D Juric","year":"2015","unstructured":"Juric D et al (2015) Convergent loss of PTEN leads to clinical resistance to a PI(3)Kalpha inhibitor. Nature 518:240\u2013244","journal-title":"Nature"},{"key":"7660_CR29","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1158\/2159-8290.CD-18-0830","volume":"10","author":"C Costa","year":"2020","unstructured":"Costa C et al (2020) PTEN loss mediates clinical cross-resistance to CDK4\/6 and PI3Kalpha inhibitors in breast cancer. Cancer Discov 10:72\u201385","journal-title":"Cancer Discov"},{"key":"7660_CR30","doi-asserted-by":"publisher","first-page":"R40","DOI":"10.1186\/bcr2594","volume":"12","author":"CJ Creighton","year":"2010","unstructured":"Creighton CJ et al (2010) Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor (ER) levels and activity in ER+ breast cancer. Breast Cancer Res 12:R40","journal-title":"Breast Cancer Res"},{"key":"7660_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2023.113397","volume":"195","author":"S Morganti","year":"2023","unstructured":"Morganti S et al (2023) Clinicopathological features and survival outcomes of luminal-like breast tumors with estrogen receptor loss at metastatic recurrence: a case-control study. Eur J Cancer 195:113397","journal-title":"Eur J Cancer"}],"container-title":["Breast Cancer Research and Treatment"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10549-025-07660-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10549-025-07660-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10549-025-07660-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T23:16:21Z","timestamp":1744845381000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10549-025-07660-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,10]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["7660"],"URL":"https:\/\/doi.org\/10.1007\/s10549-025-07660-3","relation":{},"ISSN":["0167-6806","1573-7217"],"issn-type":[{"value":"0167-6806","type":"print"},{"value":"1573-7217","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,10]]},"assertion":[{"value":"22 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 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 that there is no conflict of interest regarding the publication of this paper.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was approved by the IRB at Yale University. This study was retrospective in nature and all information was properly de-identified, therefore ethics approval and consent were waived.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}]}}