{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:35:56Z","timestamp":1788348956051,"version":"build-2803163510"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":21,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Young Scholars Fostering Fund of the First Affiliated Hospital of Nanjing Medical University","award":["PY2022040"],"award-info":[{"award-number":["PY2022040"]}]},{"name":"Young Scholars Fostering Fund of the First Affiliated Hospital of Nanjing Medical University","award":["PY2022038"],"award-info":[{"award-number":["PY2022038"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303044"],"award-info":[{"award-number":["82303044"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Young Scientist Program of Jiangsu Provincial People's Hospital","award":["CZ0121002010037"],"award-info":[{"award-number":["CZ0121002010037"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Amino Acids"],"DOI":"10.1007\/s00726-025-03494-x","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T03:52:45Z","timestamp":1765857165000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of the clinical characteristics and potentially prognostic factors in HER2-positive breast cancer"],"prefix":"10.1007","volume":"58","author":[{"given":"Liang","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Wen","family":"Xi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"3494_CR1","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1210\/er.2006-0045","volume":"29","author":"G Arpino","year":"2008","unstructured":"Arpino G, Wiechmann L, Osborne CK et al (2008) Crosstalk between the estrogen receptor and the HER tyrosine kinase receptor family: molecular mechanism and clinical implications for endocrine therapy resistance. Endocr Rev 29:217\u2013233","journal-title":"Endocr Rev"},{"key":"3494_CR2","first-page":"250","volume":"33","author":"S Bhalla","year":"1990","unstructured":"Bhalla S, Chattree N (1990) Value of clinico-pathological factors in prognosis of breast cancer patients. Indian J Pathol Microbiol 33:250\u2013257","journal-title":"Indian J Pathol Microbiol"},{"key":"3494_CR3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000279","volume":"7","author":"FM Blows","year":"2010","unstructured":"Blows FM, Driver KE, Schmidt MK et al (2010) Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies. PLoS Med 7:e1000279","journal-title":"PLoS Med"},{"key":"3494_CR4","doi-asserted-by":"publisher","DOI":"10.1186\/s40169-016-0088-3","volume":"5","author":"EL Cavalieri","year":"2016","unstructured":"Cavalieri EL, Rogan EG (2016) Depurinating estrogen-DNA adducts, generators of cancer initiation: their minimization leads to cancer prevention. Clin Transl Med 5:12","journal-title":"Clin Transl Med"},{"key":"3494_CR5","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1016\/j.ctrv.2011.11.005","volume":"38","author":"P Eroles","year":"2012","unstructured":"Eroles P, Bosch A, P\u00e9rez-Fidalgo JA et al (2012) Molecular biology in breast cancer: intrinsic subtypes and signaling pathways. Cancer Treat Rev 38:698\u2013707","journal-title":"Cancer Treat Rev"},{"key":"3494_CR6","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1016\/S1470-2045(24)00128-1","volume":"25","author":"T Fehm","year":"2024","unstructured":"Fehm T, Cottone F, Dunton K et al (2024) Trastuzumab deruxtecan versus treatment of physician\u2019s choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol 25:614\u2013625","journal-title":"Lancet Oncol"},{"key":"3494_CR7","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.ctrv.2014.01.001","volume":"40","author":"E Garattini","year":"2014","unstructured":"Garattini E, Bolis M, Garattini SK et al (2014) Retinoids and breast cancer: from basic studies to the clinic and back again. Cancer Treat Rev 40:739\u2013749","journal-title":"Cancer Treat Rev"},{"key":"3494_CR8","doi-asserted-by":"publisher","first-page":"2206","DOI":"10.1093\/annonc\/mdt303","volume":"24","author":"A Goldhirsch","year":"2013","unstructured":"Goldhirsch A, Winer EP, Coates AS et al (2013) Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 24:2206\u20132223","journal-title":"Ann Oncol"},{"key":"3494_CR9","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1586\/era.09.124","volume":"9","author":"V Guarneri","year":"2009","unstructured":"Guarneri V (2009) Lapatinib plus letrozole for postmenopausal patients with advanced HER2(+)\/HR(+) breast cancer. Expert Rev Anticancer Ther 9:1549\u20131557","journal-title":"Expert Rev Anticancer Ther"},{"key":"3494_CR10","doi-asserted-by":"publisher","first-page":"2784","DOI":"10.1200\/JCO.2009.25.6529","volume":"28","author":"ME Hammond","year":"2010","unstructured":"Hammond ME, Hayes DF, Dowsett M et al (2010) American Society of Clinical Oncology\/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28:2784\u20132795","journal-title":"J Clin Oncol"},{"key":"3494_CR11","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1002\/1097-0142(19940801)74:3+<1111::AID-CNCR2820741520>3.0.CO;2-L","volume":"74","author":"BS Hulka","year":"1994","unstructured":"Hulka BS, Liu ET, Lininger RA (1994) Steroid hormones and risk of breast cancer. Cancer 74:1111\u20131124","journal-title":"Cancer"},{"key":"3494_CR12","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.1056\/NEJMoa2108873","volume":"385","author":"K Kalinsky","year":"2021","unstructured":"Kalinsky K, Barlow WE, Gralow JR et al (2021) 21-gene assay to inform chemotherapy benefit in node-positive breast cancer. N Engl J Med 385:2336\u20132347","journal-title":"N Engl J Med"},{"key":"3494_CR13","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.2217\/fon-2020-0504","volume":"17","author":"C Kay","year":"2021","unstructured":"Kay C, Mart\u00ednez-P\u00e9rez C, Meehan J et al (2021) Current trends in the treatment of HR+\/HER2+ breast cancer. Future Oncol 17:1665\u20131681","journal-title":"Future Oncol"},{"key":"3494_CR14","doi-asserted-by":"publisher","first-page":"R62","DOI":"10.1186\/bcr2625","volume":"12","author":"DC Koay","year":"2010","unstructured":"Koay DC, Zerillo C, Narayan M et al (2010) Anti-tumor effects of retinoids combined with trastuzumab or tamoxifen in breast cancer cells: induction of apoptosis by retinoid\/trastuzumab combinations. Breast Cancer Res 12:R62","journal-title":"Breast Cancer Res"},{"key":"3494_CR15","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/S1470-2045(17)30021-9","volume":"18","author":"A Llombart-Cussac","year":"2017","unstructured":"Llombart-Cussac A, Cort\u00e9s J, Par\u00e9 L et al (2017) HER2-enriched subtype as a predictor of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage HER2-positive breast cancer (PAMELA): an open-label, single-group, multicentre, phase 2 trial. Lancet Oncol 18:545\u2013554","journal-title":"Lancet Oncol"},{"key":"3494_CR16","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/s41571-023-00849-9","volume":"21","author":"A Marra","year":"2024","unstructured":"Marra A, Chandarlapaty S, Modi S (2024) Management of patients with advanced-stage HER2-positive breast cancer: current evidence and future perspectives. Nat Rev Clin Oncol 21:185\u2013202","journal-title":"Nat Rev Clin Oncol"},{"key":"3494_CR17","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1101\/gr.239244.118","volume":"28","author":"A Mayakonda","year":"2018","unstructured":"Mayakonda A, Lin DC, Assenov Y et al (2018) Maftools: efficient and comprehensive analysis of somatic variants in cancer. Genome Res 28:1747\u20131756","journal-title":"Genome Res"},{"key":"3494_CR18","doi-asserted-by":"publisher","first-page":"17847","DOI":"10.1038\/s41598-019-54371-z","volume":"9","author":"EK Park","year":"2019","unstructured":"Park EK, Lee KS, Seo BK et al (2019) Machine learning approaches to radiogenomics of breast cancer using low-dose perfusion computed tomography: predicting prognostic biomarkers and molecular subtypes. Sci Rep 9:17847","journal-title":"Sci Rep"},{"key":"3494_CR19","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41523-023-00533-2","volume":"9","author":"M Pegram","year":"2023","unstructured":"Pegram M, Jackisch C, Johnston SRD (2023) Estrogen\/HER2 receptor crosstalk in breast cancer: combination therapies to improve outcomes for patients with hormone receptor-positive\/HER2-positive breast cancer. NPJ Breast Cancer 9:45","journal-title":"NPJ Breast Cancer"},{"key":"3494_CR20","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1200\/JCO.23.01994","volume":"42","author":"P Rastogi","year":"2024","unstructured":"Rastogi P, O\u2019Shaughnessy J, Martin M et al (2024) Adjuvant abemaciclib plus endocrine therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative, high-risk early breast cancer: results from a preplanned monarchE overall survival interim analysis, including 5-year efficacy outcomes. J Clin Oncol 42:987\u2013993","journal-title":"J Clin Oncol"},{"key":"3494_CR21","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie ME, Phipson B, Wu D et al (2015) limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 43:e47","journal-title":"Nucleic Acids Res"},{"key":"3494_CR22","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1038\/sj.onc.1209377","volume":"25","author":"C Rodriguez-Antona","year":"2006","unstructured":"Rodriguez-Antona C, Ingelman-Sundberg M (2006) Cytochrome P450 pharmacogenetics and cancer. Oncogene 25:1679\u20131691","journal-title":"Oncogene"},{"key":"3494_CR23","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1093\/annonc\/mdt595","volume":"25","author":"M Schmidt","year":"2014","unstructured":"Schmidt M, Untch M (2014) Prediction of benefit from chemotherapy in ER-positive\/HER2-negative breast cancer\u2013a problem still to be solved. Ann Oncol 25:754","journal-title":"Ann Oncol"},{"key":"3494_CR24","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1007\/s12282-024-01583-5","volume":"31","author":"Y Shang","year":"2024","unstructured":"Shang Y, Wang X, Liu Y et al (2024) Comparing survival outcomes between neoadjuvant and adjuvant chemotherapy within T2N1M0 stage hormone receptor-positive, HER2-negative breast cancer: a retrospective cohort study based on SEER database. Breast Cancer 31:684\u2013694","journal-title":"Breast Cancer"},{"key":"3494_CR25","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1007\/s00018-004-4002-6","volume":"61","author":"AM Simeone","year":"2004","unstructured":"Simeone AM, Tari AM (2004) How retinoids regulate breast cancer cell proliferation and apoptosis. Cell Mol Life Sci 61:1475\u20131484","journal-title":"Cell Mol Life Sci"},{"key":"3494_CR26","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.breast.2010.11.003","volume":"20","author":"MS Singh","year":"2011","unstructured":"Singh MS, Francis PA, Michael M (2011) Tamoxifen, cytochrome P450 genes and breast cancer clinical outcomes. Breast 20:111\u2013118","journal-title":"Breast"},{"key":"3494_CR27","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209\u2013249","journal-title":"CA Cancer J Clin"},{"key":"3494_CR28","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1200\/JCO.2006.09.2775","volume":"25","author":"AC Wolff","year":"2007","unstructured":"Wolff AC, Hammond ME, Schwartz JN et al (2007) American Society of Clinical Oncology\/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118\u2013145","journal-title":"J Clin Oncol"},{"key":"3494_CR29","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.jsbmb.2015.05.005","volume":"153","author":"VS Wu","year":"2015","unstructured":"Wu VS, Kanaya N, Lo C et al (2015) From bench to bedside: what do we know about hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer? J Steroid Biochem Mol Biol 153:45\u201353","journal-title":"J Steroid Biochem Mol Biol"},{"key":"3494_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116615","volume":"175","author":"S Yan","year":"2024","unstructured":"Yan S, Ji J, Zhang Z et al (2024) Targeting the crosstalk between estrogen receptors and membrane growth factor receptors in breast cancer treatment: advances and opportunities. Biomed Pharmacother 175:116615","journal-title":"Biomed Pharmacother"},{"key":"3494_CR31","doi-asserted-by":"publisher","first-page":"2612","DOI":"10.1038\/ncomms3612","volume":"4","author":"K Yoshihara","year":"2013","unstructured":"Yoshihara K, Shahmoradgoli M, Mart\u00ednez E et al (2013) Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun 4:2612","journal-title":"Nat Commun"},{"key":"3494_CR32","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.602555","volume":"10","author":"JA Zhang","year":"2020","unstructured":"Zhang JA, Zhou XY, Huang D et al (2020) Development of an immune-related gene signature for prognosis in melanoma. Front Oncol 10:602555","journal-title":"Front Oncol"},{"key":"3494_CR33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0280474","volume":"18","author":"H Zheng","year":"2023","unstructured":"Zheng H, Ge C, Lin H et al (2023) The impact of age on outcomes of breast cancer in different hormone receptor and HER2 groups. PLoS ONE 18:e0280474","journal-title":"PLoS ONE"}],"container-title":["Amino Acids"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00726-025-03494-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00726-025-03494-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00726-025-03494-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T15:48:10Z","timestamp":1767714490000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00726-025-03494-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,16]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3494"],"URL":"https:\/\/doi.org\/10.1007\/s00726-025-03494-x","relation":{},"ISSN":["1438-2199"],"issn-type":[{"value":"1438-2199","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,16]]},"assertion":[{"value":"21 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 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":"Conflict of interest"}},{"value":"Not applicable. This article does not contain any studies involving human participants or animals performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"4"}}