{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:56:46Z","timestamp":1791280606612,"version":"4.1.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":67,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CP23\/00002"],"award-info":[{"award-number":["CP23\/00002"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CP20\/00119"],"award-info":[{"award-number":["CP20\/00119"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Novartis Spain"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Precis. Onc."],"DOI":"10.1038\/s41698-026-01546-3","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:43:45Z","timestamp":1785523425000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Concordance analysis of non-invasive techniques for PIK3CA and ESR1 mutations in advanced HR+\/HER2- breast cancer: the CANIPE study"],"prefix":"10.1038","volume":"10","author":[{"given":"Clotilde","family":"Costa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n Manuel","family":"Lago-Lest\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aitor","family":"Rodr\u00edguez-Casanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Curiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Abalo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Abu\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Palacios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Cueva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Carmona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Cortegoso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seraf\u00edn","family":"Morales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Gum\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kepa","family":"Amillano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana L\u00f3pez","family":"Flores","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaura Fern\u00e1ndez","family":"P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio Fern\u00e1ndez","family":"Sobrado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Gi\u00f3n","family":"Cort\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Pena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Garc\u00eda-Mata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Saenz de Miera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel","family":"D\u00edaz-Lagares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Muinelo-Romay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"L\u00f3pez-L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"1546_CR1","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/S0140-6736(20)30165-3","volume":"395","author":"LM Spring","year":"2020","unstructured":"Spring, L. M. et al. Cyclin-dependent kinase 4 and 6 inhibitors for hormone receptor-positive breast cancer: past, present, and future. Lancet 395, 817\u2013827 (2020).","journal-title":"Lancet"},{"key":"1546_CR2","doi-asserted-by":"publisher","first-page":"5218","DOI":"10.1158\/1078-0432.CCR-17-0754","volume":"23","author":"MN Dickler","year":"2017","unstructured":"Dickler, M. N. et al. MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR+\/HER2- metastatic breast cancer. Clin. Cancer Res. 23, 5218\u20135224 (2017).","journal-title":"Clin. Cancer Res."},{"key":"1546_CR3","doi-asserted-by":"publisher","first-page":"3638","DOI":"10.1200\/JCO.2017.75.6155","volume":"35","author":"MP Goetz","year":"2017","unstructured":"Goetz, M. P. et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J. Clin. Oncol. 35, 3638\u20133646 (2017).","journal-title":"J. Clin. Oncol."},{"key":"1546_CR4","doi-asserted-by":"crossref","unstructured":"O\u2019leary B. et al. The genetic landscape and clonal evolution of breast cancer resistance to palbociclib plus fulvestrant in the PALOMA-3 trial. Cancer Discov. 8, 1390\u20131403 (2018).","DOI":"10.1158\/2159-8290.CD-18-0264"},{"key":"1546_CR5","doi-asserted-by":"publisher","first-page":"2465","DOI":"10.1200\/JCO.2018.78.9909","volume":"36","author":"DJ Slamon","year":"2018","unstructured":"Slamon, D. J. et al. Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J. Clin. Oncol. 36, 2465\u20132472 (2018).","journal-title":"J. Clin. Oncol."},{"key":"1546_CR6","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1093\/annonc\/mdy155","volume":"29","author":"GN Hortobagyi","year":"2018","unstructured":"Hortobagyi, G. N. et al. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann. Oncol. 29, 1541\u20131547 (2018).","journal-title":"Ann. Oncol."},{"key":"1546_CR7","doi-asserted-by":"crossref","unstructured":"Papadimitriou, M. C. et al. Resistance to CDK4\/6 inhibition: Mechanisms and strategies to overcome a therapeutic problem in the treatment of hormone receptor-positive metastatic breast cancer. Biochim. Biophys. Acta Mol Cell Res. 1869, 119346 (2022).","DOI":"10.1016\/j.bbamcr.2022.119346"},{"key":"1546_CR8","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1158\/2159-8290.CD-19-1390","volume":"10","author":"SA Wander","year":"2020","unstructured":"Wander, S. A. et al. The genomic landscape of intrinsic and acquired resistance to cyclin-dependent kinase 4\/6 inhibitors in patients with hormone receptor\u2013positive metastatic breast cancer. Cancer Discov. 10, 1174\u20131193 (2020).","journal-title":"Cancer Discov."},{"key":"1546_CR9","doi-asserted-by":"publisher","first-page":"TPS618","DOI":"10.1200\/JCO.2016.34.15_suppl.TPS618","volume":"34","author":"F Andre","year":"2016","unstructured":"Andre, F. et al. SOLAR-1: a phase III study of alpelisib + fulvestrant in men and postmenopausal women with HR+\/HER2\u2013 advanced breast cancer (BC) progressing on or after prior aromatase inhibitor therapy. J. Clin. Oncol. 34, TPS618\u2013TPS618 (2016).","journal-title":"J. Clin. Oncol."},{"key":"1546_CR10","doi-asserted-by":"publisher","DOI":"10.1200\/GO.23.00285","volume":"10","author":"S Al Sukhun","year":"2024","unstructured":"Al Sukhun, S. et al. Systemic treatment of patients with metastatic breast cancer: ASCO resource\u2013stratified guideline. JCO Glob. Oncol. 10, e2300285 (2024).","journal-title":"JCO Glob. Oncol."},{"key":"1546_CR11","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.SABCS22-GS3-01","volume":"83","author":"A Bardia","year":"2023","unstructured":"Bardia, A. et al. Abstract GS3-01: GS3-01 EMERALD phase 3 trial of elacestrant versus standard of care endocrine therapy in patients with ER+\/HER2- metastatic breast cancer: updated results by duration of prior CDK4\/6i in metastatic setting. Cancer Res. 83, GS3-01 (2023).","journal-title":"Cancer Res."},{"key":"1546_CR12","doi-asserted-by":"publisher","first-page":"2058","DOI":"10.1056\/NEJMoa2214131","volume":"388","author":"NC Turner","year":"2023","unstructured":"Turner, N. C. et al. Capivasertib in hormone receptor\u2013positive advanced breast cancer. N. Engl. J. Med. 388, 2058\u20132070 (2023).","journal-title":"N. Engl. J. Med."},{"key":"1546_CR13","doi-asserted-by":"crossref","unstructured":"Pascual, J. et al. ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group. Ann. Oncol. 33, 750\u2013768 (2022).","DOI":"10.1016\/j.annonc.2022.05.520"},{"key":"1546_CR14","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2024.104427","volume":"201","author":"E Guerini-Rocco","year":"2024","unstructured":"Guerini-Rocco, E. et al. Standardized molecular pathology workflow for ctDNA-based ESR1 testing in HR+\/HER2\u2212 metastatic breast cancer. Crit. Rev. Oncol. Hematol. 201, 104427 (2024).","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"1546_CR15","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1158\/2159-8290.CD-18-1084","volume":"8","author":"R Schiff","year":"2018","unstructured":"Schiff, R. & Jeselsohn, R. Is ctDNA the road map to the landscape of the clonal mutational evolution in drug resistance? Lessons from the PALOMA-3 study and implications for precision medicine. Cancer Discov. 8, 1352\u20131354 (2018).","journal-title":"Cancer Discov."},{"key":"1546_CR16","doi-asserted-by":"crossref","unstructured":"Gerratana, L. et al. Interplay between ESR1\/PIK3CA codon variants, oncogenic pathway alterations and clinical phenotype in patients with metastatic breast cancer (MBC): comprehensive circulating tumor DNA (ctDNA) analysis. Breast Cancer Res. 25, 112 (2023).","DOI":"10.1186\/s13058-023-01718-0"},{"key":"1546_CR17","doi-asserted-by":"crossref","unstructured":"Darrigues, L. et al. Abstract P4-01-20: circulating tumor DNA as a predictive biomarker of response to palbociclib-fulvestrant in patients with estrogen receptor-positive, HER2-negative metastatic breast cancer. Cancer Res. 23, 31 (2019).","DOI":"10.1158\/1538-7445.SABCS18-P4-01-20"},{"key":"1546_CR18","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1158\/1078-0432.CCR-21-3276","volume":"28","author":"SM Tolaney","year":"2022","unstructured":"Tolaney, S. M. et al. Clinical significance of PIK3CA and ESR1 mutations in circulating tumor DNA: analysis from the MONARCH 2 study of abemaciclib plus fulvestrant. Clin. Cancer Res. 28, 1500\u20131506 (2022).","journal-title":"Clin. Cancer Res."},{"key":"1546_CR19","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1056\/NEJMoa1813904","volume":"380","author":"F Andr\u00e9","year":"2019","unstructured":"Andr\u00e9, F. et al. Alpelisib for PIK3CA -mutated, hormone receptor\u2013positive advanced breast cancer. N. Engl. J. Med. 380, 1929\u20131940 (2019).","journal-title":"N. Engl. J. Med."},{"key":"1546_CR20","doi-asserted-by":"crossref","unstructured":"Schiavon, G. et al. Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. Sci. Transl. Med. 7, 313ra182 (2015).","DOI":"10.1126\/scitranslmed.aac7551"},{"key":"1546_CR21","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1056\/NEJMoa2502929","volume":"393","author":"FC Bidard","year":"2025","unstructured":"Bidard, F. C. et al. First-line camizestrant for emerging ESR1-mutated advanced breast cancer. N. Engl. J. Med. 393, 569\u2013580 (2025).","journal-title":"N. Engl. J. Med."},{"key":"1546_CR22","unstructured":"Burstein, H. J., Demichele, A., Fallowfield, L., Somerfield, M. R. & Lynn Henry, N. Endocrine and targeted therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer - capivasertib-fulvestrant: ASCO rapid recommendation update. J. Clin. Oncol. 42, 1450\u20131453 (2024)."},{"key":"1546_CR23","doi-asserted-by":"crossref","unstructured":"Suppan, C. et al. Sensitive and robust liquid biopsy-based detection of PIK3CA mutations in hormone-receptor-positive metastatic breast cancer patients. Br. J. Cancer. 126, 456\u2013463 (2021).","DOI":"10.1038\/s41416-021-01601-9"},{"key":"1546_CR24","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1111\/cge.14077","volume":"101:","author":"G Duque","year":"2022","unstructured":"Duque, G. et al. Clinical utility of liquid biopsy in breast cancer: a systematic review. Clin. Genet. 101:, 285\u2013295 (2022).","journal-title":"Clin. Genet."},{"key":"1546_CR25","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1272\/jnms.JNMS.2022_89-107","volume":"89","author":"M Nakai","year":"2022","unstructured":"Nakai, M. et al. Use of liquid biopsy to detect PIK3CA mutation in metastatic breast cancer. J. Nippon Med. Sch. 89, 66\u201371 (2022).","journal-title":"J. Nippon Med. Sch."},{"key":"1546_CR26","doi-asserted-by":"publisher","first-page":"625636","DOI":"10.3389\/fonc.2021.625636","volume":"11","author":"L Urso","year":"2021","unstructured":"Urso, L. et al. ESR1 Gene mutation in hormone receptor-positive HER2-negative metastatic breast cancer patients: concordance between tumor tissue and circulating tumor DNA analysis. Front. Oncol. 11, 625636 (2021).","journal-title":"Front. Oncol."},{"key":"1546_CR27","unstructured":"Page, K. et al. Circulating tumor DNA profiling from breast cancer screening through to metastatic disease. JCO Precis. Oncol. 5, PO.20.00522 (2021)."},{"key":"1546_CR28","doi-asserted-by":"crossref","unstructured":"Anderson, E. J. et al. A systematic review of the prevalence and diagnostic workup of PIK3CA mutations in HR+\/HER2- metastatic breast cancer. Int. J. Breast Cancer. 2020, 3759179 (2020).","DOI":"10.1155\/2020\/3759179"},{"key":"1546_CR29","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1007\/s10549-024-07376-w","volume":"207","author":"MA Bhave","year":"2024","unstructured":"Bhave, M. A. et al. Comprehensive genomic profiling of ESR1, PIK3CA, AKT1, and PTEN in HR(+)HER2(-) metastatic breast cancer: prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice. Breast Cancer Res. Treat. 207, 599\u2013609 (2024).","journal-title":"Breast Cancer Res. Treat."},{"key":"1546_CR30","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-020-07445-5","volume":"20","author":"S Verma","year":"2020","unstructured":"Verma, S. et al. Analytical performance evaluation of a commercial next generation sequencing liquid biopsy platform using plasma ctDNA, reference standards, and synthetic serial dilution samples derived from normal plasma. BMC Cancer 20, 945 (2020).","journal-title":"BMC Cancer"},{"key":"1546_CR31","doi-asserted-by":"crossref","unstructured":"Schouten, R. D. et al. Clinical Utility of plasma-based comprehensive molecular profiling in advanced non\u2013small-cell lung cancer. JCO Precis. Oncol. 5, 1112\u20131121 (2021).","DOI":"10.1200\/PO.20.00450"},{"key":"1546_CR32","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-022-03421-8","volume":"20","author":"H Liao","year":"2022","unstructured":"Liao, H. et al. Identification of mutation patterns and circulating tumour DNA-derived prognostic markers in advanced breast cancer patients. J. Transl. Med. 20, 211 (2022).","journal-title":"J. Transl. Med."},{"key":"1546_CR33","doi-asserted-by":"publisher","first-page":"4166","DOI":"10.1158\/1078-0432.CCR-23-0956","volume":"29","author":"J Pascual","year":"2023","unstructured":"Pascual, J. et al. Baseline mutations and ctDNA dynamics as prognostic and predictive factors in ER-positive\/HER2-negative metastatic breast cancer patients. Clin. Cancer Res. 29, 4166\u20134177 (2023).","journal-title":"Clin. Cancer Res."},{"key":"1546_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-021-00202-2","volume":"5","author":"JD Finkle","year":"2021","unstructured":"Finkle, J. D. et al. Validation of a liquid biopsy assay with molecular and clinical profiling of circulating tumor DNA. NPJ Precis. Oncol. 5, 63 (2021).","journal-title":"NPJ Precis. Oncol."},{"key":"1546_CR35","doi-asserted-by":"publisher","first-page":"105241","DOI":"10.1016\/j.phrs.2020.105241","volume":"163","author":"M Del Re","year":"2021","unstructured":"Del Re, M. et al. PI3K mutations detected in liquid biopsy are associated to reduced sensitivity to CDK4\/6 inhibitors in metastatic breast cancer patients. Pharm. Res. 163, 105241 (2021).","journal-title":"Pharm. Res."},{"key":"1546_CR36","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-019-1235-8","volume":"21","author":"D Fernandez-Garcia","year":"2019","unstructured":"Fernandez-Garcia, D. et al. Plasma cell-free DNA (cfDNA) as a predictive and prognostic marker in patients with metastatic breast cancer. Breast Cancer Res. 21, 149 (2019).","journal-title":"Breast Cancer Res."},{"key":"1546_CR37","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-77","volume":"12","author":"X Robin","year":"2011","unstructured":"Robin, X. et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics 12, 77 (2011).","journal-title":"BMC Bioinformatics"}],"container-title":["npj Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41698-026-01546-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41698-026-01546-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41698-026-01546-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:41:00Z","timestamp":1791279660000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41698-026-01546-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1546"],"URL":"https:\/\/doi.org\/10.1038\/s41698-026-01546-3","relation":{},"ISSN":["2397-768X"],"issn-type":[{"value":"2397-768X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]},"assertion":[{"value":"20 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Rafael L\u00f3pez (R.L.). reports grants and personal fees from Roche, Merck, AstraZeneca, Bayer, Pharmamar, and Leo, and personal fees and nonfinancial support from Bristol-Myers Squibb and Novartis, outside of the submitted work. The remaining authors declare no competing financial or nonfinancial interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"375"}}