{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T08:55:18Z","timestamp":1787993718702,"version":"build-2784847793"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"published-print":{"date-parts":[[2021,10]]},"DOI":"10.1007\/s00428-021-03104-7","type":"journal-article","created":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T14:41:16Z","timestamp":1620052876000},"page":"853-857","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Is there a correlation between HER2 gene amplification level and response to neoadjuvant treatment with trastuzumab and chemotherapy in HER2-positive breast cancer?"],"prefix":"10.1007","volume":"479","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0110-3349","authenticated-orcid":false,"given":"Silvia","family":"Antol\u00edn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0116-1263","authenticated-orcid":false,"given":"Luc\u00eda","family":"Garc\u00eda-Caballero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Reboredo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurea","family":"Molina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"Mosquera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel","family":"V\u00e1zquez-Boquete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosal\u00eda","family":"Gallego","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari Paz","family":"Santiago","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel","family":"Concha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0498-7626","authenticated-orcid":false,"given":"Eva","family":"P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8314-0241","authenticated-orcid":false,"given":"Lourdes","family":"Calvo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7938-1437","authenticated-orcid":false,"given":"Tom\u00e1s","family":"Garc\u00eda-Caballero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,1]]},"reference":[{"key":"3104_CR1","doi-asserted-by":"publisher","first-page":"2659","DOI":"10.1200\/JCO.1998.16.8.2659","volume":"16","author":"MD Pegram","year":"1998","unstructured":"Pegram MD, Lipton A, Hayes DF, Weber BL, Baselga JM, Tripathy D, Baly D, Baughman SA, Twaddell T, Glaspy JA, Slamon DJ (1998) Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2\/neu monoclonal antibody plus cisplatin in patients with HER2\/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J Clin Oncol 16:2659\u20132671. https:\/\/doi.org\/10.1200\/JCO.1998.16.8.2659","journal-title":"J Clin Oncol"},{"key":"3104_CR2","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S1470-2045(11)70336-9","volume":"13","author":"L Gianni","year":"2012","unstructured":"Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P (2012) Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 13:25\u201332. https:\/\/doi.org\/10.1016\/S1470-2045(11)70336-9","journal-title":"Lancet Oncol"},{"key":"3104_CR3","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/S0140-6736(11)61847-3","volume":"379","author":"J Baselga","year":"2012","unstructured":"Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, G\u00f3mez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horv\u00e1th Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M, NeoALTTO Study Team (2012) Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 379:633\u2013640. https:\/\/doi.org\/10.1016\/S0140-6736(11)61847-3","journal-title":"Lancet"},{"key":"3104_CR4","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.1200\/JCO.2005.02.8886","volume":"24","author":"J Hurley","year":"2006","unstructured":"Hurley J, Doliny P, Reis I, Silva O, Gomez-Fernandez C, Velez P, Pauletti G, Powell JE, Pegram MD, Slamon DJ (2006) Docetaxel, cisplatin, and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2-positive locally advanced breast cancer. J Clin Oncol 24:1831\u20131838. https:\/\/doi.org\/10.1200\/JCO.2005.02.8886","journal-title":"J Clin Oncol"},{"key":"3104_CR5","doi-asserted-by":"publisher","first-page":"2962","DOI":"10.1200\/JCO.2008.19.7939","volume":"27","author":"M Dowsett","year":"2009","unstructured":"Dowsett M, Procter M, McCaskill-Stevens W, de Azambuja E, Dafni U, Ruschoff J, Jordan B, Dolci S, Abramovitz M, Stoss O, Viale G, Gelber RD, Piccart-Gebhart M, Leyland-Jones B (2009) Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA Trial. J Clin Oncol 27:2962\u20132969. https:\/\/doi.org\/10.1200\/JCO.2008.19.7939","journal-title":"J Clin Oncol"},{"key":"3104_CR6","doi-asserted-by":"publisher","first-page":"4307","DOI":"10.1200\/JCO.2009.26.2154","volume":"28","author":"EA Perez","year":"2010","unstructured":"Perez EA, Reinholz MM, Hillman DW, Tenner KS, Schroeder MJ, Davidson NE, Martino S, Sledge GW, Harris LN, Gralow JR, Dueck AC, Ketterling RP, Ingle JN, Lingle WL, Kaufman PA, Visscher DW, Jenkins RB (2010) HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial. J Clin Oncol 28:4307\u20134315. https:\/\/doi.org\/10.1200\/JCO.2009.26.2154","journal-title":"J Clin Oncol"},{"key":"3104_CR7","doi-asserted-by":"publisher","first-page":"6404","DOI":"10.1158\/1078-0432.CCR-06-3022","volume":"13","author":"L Arnould","year":"2007","unstructured":"Arnould L, Arveux P, Couturier J, Gelly-Marty M, Loustalot C, Ettore F, Sagan C, Antoine M, Penault-Llorca F, Vasseur B, Fumoleau P, Coudert BP (2007) Pathologic complete response to trastuzumab-based neoadjuvant therapy is related to the level of HER-2 amplification. Clin Cancer Res 13:6404\u20136409. https:\/\/doi.org\/10.1158\/1078-0432.CCR-06-3022","journal-title":"Clin Cancer Res"},{"key":"3104_CR8","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/j.ejca.2006.11.019","volume":"43","author":"R Giuliani","year":"2007","unstructured":"Giuliani R, Durbecq V, Di Leo A, Paesmans M, Larsimont D, Leroy JY, Borms M, Vindevoghel A, Jerusalem G, D\u2019Hondt V, Dirix L, Canon JL, Richard V, Cocquyt V, Majois F, Reginster M, Demol J, Kains JP, Delree P, Keppens C, Sotiriou C, Piccart MJ, Cardoso F (2007) Phosphorylated HER-2 tyrosine kinase and Her-2\/neu gene amplification as predictive factors of response to trastuzumab in patients with HER-2 overexpressing metastatic breast cancer (MBC). Eur J Cancer 43:725\u2013735. https:\/\/doi.org\/10.1016\/j.ejca.2006.11.019","journal-title":"Eur J Cancer"},{"key":"3104_CR9","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1002\/ijc.28660","volume":"135","author":"EM Fuchs","year":"2014","unstructured":"Fuchs EM, K\u00f6stler WJ, Horvat R, Hudelist G, Kubista E, Attems J, Zielinski CC, Singer CF (2014) High-level ERBB2 gene amplification is associated with a particularly short time-to-metastasis, but results in a high rate of complete response once trastuzumab-based therapy is offered in the metastatic setting. Int J Cancer 135:224\u2013231. https:\/\/doi.org\/10.1002\/ijc.28660","journal-title":"Int J Cancer"},{"key":"3104_CR10","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/s0960-9776(03)00106-1","volume":"12","author":"KN Ogston","year":"2003","unstructured":"Ogston KN, Miller D, Payne S, Hutcheon AW, Sarkar TK, Smith I, Schofield A, Heys SD (2003) A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast 12:320\u2013327. https:\/\/doi.org\/10.1016\/s0960-9776(03)00106-1","journal-title":"Breast"},{"key":"3104_CR11","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.clbc.2019.09.003","volume":"20","author":"JL Meisel","year":"2020","unstructured":"Meisel JL, Zhao J, Suo A, Zhang C, Wei Z, Taylor C, Aneja R, Krishnamurti U, Li Z, Nahta R, O\u2019Regan R, Li X (2020) Clinicopathologic factors associated with response to neoadjuvant anti-HER2-directed chemotherapy in HER2-positive breast cancer. Clin Breast Cancer 20:19\u201324. https:\/\/doi.org\/10.1016\/j.clbc.2019.09.003","journal-title":"Clin Breast Cancer"},{"key":"3104_CR12","doi-asserted-by":"publisher","first-page":"3676","DOI":"10.1158\/1078-0432.CCR-16-2373","volume":"23","author":"CF Singer","year":"2017","unstructured":"Singer CF, Tan YY, Fitzal F, Steger GG, Egle D, Reiner A, Rudas M, Moinfar F, Gruber C, Petru E, Bartsch R, Tendl KA, Fuchs D, Seifert M, Exner R, Balic M, Bago-Horvath Z, Filipits M, Gnant M, Austrian Breast and Colorectal Cancer Study Group (2017) Pathological complete response to neoadjuvant trastuzumab is dependent on HER2\/CEP17 ratio in HER2-amplified early breast cancer. Clin Cancer Res 23:3676\u20133683. https:\/\/doi.org\/10.1158\/1078-0432.CCR-16-2373","journal-title":"Clin Cancer Res"},{"key":"3104_CR13","doi-asserted-by":"publisher","first-page":"R73","DOI":"10.1186\/bcr3690","volume":"16","author":"A Schneeweiss","year":"2014","unstructured":"Schneeweiss A, Chia S, Hegg R, Tausch C, Deb R, Ratnayake J, McNally V, Ross G, Kiermaier A, Cort\u00e9s J (2014) Evaluating the predictive value of biomarkers for efficacy outcomes in response to pertuzumab- and trastuzumab-based therapy: an exploratory analysis of the TRYPHAENA study. Breast Cancer Res 16:R73. https:\/\/doi.org\/10.1186\/bcr3690","journal-title":"Breast Cancer Res"},{"key":"3104_CR14","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1093\/annonc\/mdz076","volume":"30","author":"J Veeraraghavan","year":"2019","unstructured":"Veeraraghavan J, Angelis C, Mao R, Wang T, Herrera S, Pavlick AC, Contreras A, Nuciforo P, Mayer IA, Forero A, Nanda R, Goetz MP, Chang JC, Wolff AC, Krop IE, Fuqua SAW, Prat A, Hilsenbeck SG, Weigelt B, Reis-Filho JS, Gutierrez C, Osborne CK, Rimawi MF, Schiff R (2019) A combinatorial biomarker predicts pathologic complete response to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2+ breast cancer. Ann Oncol 30:927\u2013933. https:\/\/doi.org\/10.1093\/annonc\/mdz076","journal-title":"Ann Oncol"},{"key":"3104_CR15","doi-asserted-by":"publisher","first-page":"e23053","DOI":"10.1097\/MD.0000000000023053","volume":"99","author":"JH Choi","year":"2020","unstructured":"Choi JH, Jeon CW, Kim YO, Jung S (2020) Pathological complete response to neoadjuvant trastuzumab and pertuzumab therapy is related to human epidermal growth factor receptor 2 (HER2) amplification level in HER2-amplified breast cancer. Medicine (Baltimore) 99:e23053. https:\/\/doi.org\/10.1097\/MD.0000000000023053","journal-title":"Medicine (Baltimore)"}],"updated-by":[{"DOI":"10.1007\/s00428-021-03121-6","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,6,12]],"date-time":"2021-06-12T00:00:00Z","timestamp":1623456000000}}],"container-title":["Virchows Archiv"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-021-03104-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00428-021-03104-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-021-03104-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T19:06:50Z","timestamp":1634238410000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00428-021-03104-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,1]]},"references-count":15,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["3104"],"URL":"https:\/\/doi.org\/10.1007\/s00428-021-03104-7","relation":{"correction":[{"id-type":"doi","id":"10.1007\/s00428-021-03121-6","asserted-by":"object"}]},"ISSN":["0945-6317","1432-2307"],"issn-type":[{"value":"0945-6317","type":"print"},{"value":"1432-2307","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,1]]},"assertion":[{"value":"28 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 June 2021","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s00428-021-03121-6","URL":"https:\/\/doi.org\/10.1007\/s00428-021-03121-6","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Ethics Committee of Galicia (Spain) (code: SAN-TRA-2015\u201301).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}