{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:14:22Z","timestamp":1792628062673,"version":"4.5.0"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>We present a case of a woman with epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma who received gefitinib for 2 years and obtained a partial response. The patient then developed liver metastasis and a breast lesion, displaying high estrogen receptor (ER) expression and harboring the same EGFR mutation. From the radiological studies, it was not possible to make a differential diagnosis between primary breast cancer and breast metastasis from lung cancer. After the removal of the breast nodule, thanks to the clinical history, radiology, and above all, molecular and immunohistochemical investigations, a diagnosis of breast metastasis from lung adenocarcinoma was made. This case emphasizes the importance of a comprehensive clinical, pathological, and molecular analysis in the differential diagnosis between primary breast cancer and metastases from extramammary tumor to guide adequate treatment decision making.<\/jats:p>","DOI":"10.3390\/curroncol28050292","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T08:42:32Z","timestamp":1630399352000},"page":"3384-3392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Complex Differential Diagnosis between Primary Breast Cancer and Breast Metastasis from EGFR-Mutated Lung Adenocarcinoma: Case Report and Literature Review"],"prefix":"10.3390","volume":"28","author":[{"given":"Carmine","family":"Valenza","sequence":"first","affiliation":[{"name":"Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milan, Italy"},{"name":"Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Maria","family":"Porta","sequence":"additional","affiliation":[{"name":"Division of Pathology and Laboratory Medicine, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milan, Italy"},{"name":"School of Pathology, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Rappa","sequence":"additional","affiliation":[{"name":"Division of Pathology and Laboratory Medicine, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Guerini-Rocco","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy"},{"name":"Division of Pathology and Laboratory Medicine, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Viale","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy"},{"name":"Division of Pathology and Laboratory Medicine, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0943-4804","authenticated-orcid":false,"given":"Massimo","family":"Barberis","sequence":"additional","affiliation":[{"name":"Division of Pathology and Laboratory Medicine, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"de Marinis","sequence":"additional","affiliation":[{"name":"Division of Thoracic Oncology, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1781-2518","authenticated-orcid":false,"given":"Giuseppe","family":"Curigliano","sequence":"additional","affiliation":[{"name":"Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milan, Italy"},{"name":"Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Catania","sequence":"additional","affiliation":[{"name":"Division of Thoracic Oncology, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1002\/1097-0142(20011101)92:9<2259::AID-CNCR1571>3.0.CO;2-O","article-title":"Secondary neoplasms of the breast","volume":"92","author":"Georgiannos","year":"2001","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1111\/j.1600-0463.2009.02529.x","article-title":"Secondary breast cancer: A 5-year population-based study with review of the literature","volume":"117","author":"Klingen","year":"2009","journal-title":"APMIS"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1097\/RUQ.0b013e3182a00fc4","article-title":"Lung Cancer Metastatic to Breast","volume":"29","author":"Sousaris","year":"2013","journal-title":"Ultrasound Q."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1007\/s00428-017-2262-4","article-title":"Metastatic non-small cell lung carcinoma a mimic of primary breast carcinoma\u2014Case series and literature review","volume":"472","author":"Ali","year":"2018","journal-title":"Virchows Arch."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10","DOI":"10.4103\/1742-6413.65056","article-title":"Fine-needle aspiration cytology of extra mammary metastatic lesions in the breast: A retrospective study of 36 cases diagnosed during 18 years","volume":"7","author":"Sauer","year":"2010","journal-title":"Cytojournal"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.acra.2010.12.009","article-title":"Metastases to the Breast from Non-mammary Malignancies","volume":"18","author":"Surov","year":"2011","journal-title":"Acad. Radiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1001\/archsurg.134.4.450","article-title":"An Update of Tumor Metastasis to the Breast Data","volume":"134","author":"Alva","year":"1999","journal-title":"Arch. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.jss.2014.01.024","article-title":"Metastasis of primary lung carcinoma to the breast: A systematic review of the literature","volume":"188","author":"Mirrielees","year":"2014","journal-title":"J. Surg. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.lungcan.2011.08.015","article-title":"Late breast metastasis from resected lung cancer diagnosed by epidermal growth factor receptor gene mutation","volume":"74","author":"Fukumoto","year":"2011","journal-title":"Lung Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1159\/000343678","article-title":"CBDCA + Pemetrexed + Bevacizumab and Its Maintenance Chemotherapy in a Case of Solitary Breast Metastasis from a Lung Adenocarcinoma Resistant to Gefitinib","volume":"5","author":"Sato","year":"2012","journal-title":"Case Rep. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1097\/JTO.0b013e31828f6873","article-title":"Lung Adenocarcinoma with Ipsilateral Breast Metastasis: A Simple Coincidence?","volume":"8","author":"Huang","year":"2013","journal-title":"J. Thorac. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1002\/rcr2.14","article-title":"Advanced right lung adenocarcinoma with ipsilateral breast metastasis","volume":"1","author":"Liam","year":"2013","journal-title":"Respirol. Case Rep."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Jeong, Y.J., Bong, J.G., Oh, H.K., Park, S.H., Kang, S.M., and Bae, S.H. (2014). Metachronous isolated breast metastasis from pulmonary adenocarcinoma with micropapillary component causing diagnostic challenges. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-736"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1159\/000381014","article-title":"EGFR-Mutated Breast Metastasis of Lung Adenocarcinoma: A Case Report","volume":"8","author":"Dansin","year":"2015","journal-title":"Case Rep. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"207","DOI":"10.3233\/BD-150406","article-title":"Incidental lung cancer found on screening breast MRI with eventual lymphatic metastasis to the breast","volume":"35","author":"Lee","year":"2015","journal-title":"Breast Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Lin, Q., Cai, G., Yang, K.-Y., Yang, L., Chen, C.-S., and Li, Y.-P. (2016). Case report: Small cell transformation and metastasis to the breast in a patient with lung adenocarcinoma following maintenance treatment with epidermal growth factor receptor tyrosine kinase inhibitors. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2623-4"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ninan, J., Naik, V., and George, G.M. (2016). \u2018Inflammatory breast cancer\u2019 due to metastatic adenocarcinoma of lung. BMJ Case Rep., bcr2016215857.","DOI":"10.1136\/bcr-2016-215857"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1002\/ccr3.1636","article-title":"Breast metastasis from EGFR-mutated lung adenocarcinoma: A case report and review of the literature","volume":"6","author":"Ota","year":"2018","journal-title":"Clin. Case Rep."},{"key":"ref_19","first-page":"208","article-title":"Breast metastasis from lung cancer: A report of two cases and literature review","volume":"11","author":"Wang","year":"2014","journal-title":"Cancer Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1002\/jcu.20815","article-title":"Metastases to the breast from extramammary malignancies-sonographic features","volume":"39","author":"Lee","year":"2011","journal-title":"J. Clin. Ultrasound"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0887-2171(00)90031-3","article-title":"Nonmammary malignancies of the breast: Ultrasound, CT, and MRI","volume":"21","author":"Yang","year":"2000","journal-title":"Semin. Ultrasound CT MRI"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3348\/kjr.2014.15.1.20","article-title":"Breast Metastases from Extramammary Malignancies: Typical and Atypical Ultrasound Features","volume":"15","author":"Mun","year":"2014","journal-title":"Korean J. Radiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1136\/jcp.2006.046078","article-title":"The histological diagnosis of metastases to the breast from extramammary malignancies","volume":"60","author":"Lee","year":"2006","journal-title":"J. Clin. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/his.12877","article-title":"Markers of metastatic carcinoma of breast origin","volume":"68","author":"Gown","year":"2016","journal-title":"Histopathology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/his.14141","article-title":"Histological clues to the diagnosis of metastasis to the breast from extramammary malignancies","volume":"77","author":"Lee","year":"2020","journal-title":"Histopathology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1097\/PAS.0b013e318157a5a6","article-title":"Gross Cystic Disease Fluid Protein\u2014(GCDFP-15)","volume":"32","author":"Striebel","year":"2008","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1097\/PAS.0b013e3182a0218f","article-title":"GATA3: A Multispecific But Potentially Useful Marker in Surgical Pathology","volume":"38","author":"Miettinen","year":"2014","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.prp.2005.05.010","article-title":"Napsin A is useful to distinguish primary lung adenocarcinoma from adenocarcinomas of other organs","volume":"201","author":"Suzuki","year":"2005","journal-title":"Pathol. Res. Pract."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1177\/1066896916629781","article-title":"Aberrant Expression of Napsin A in Breast Carcinoma With Apocrine Features","volume":"24","author":"Vitkovski","year":"2016","journal-title":"Int. J. Surg. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1046\/j.1365-2559.2000.00801.x","article-title":"Thyroid transcription factor-1 is the superior immunohistochemical marker for pulmonary adenocarcinomas and large cell carcinomas compared to surfactant proteins A and B","volume":"36","author":"Kaufmann","year":"2000","journal-title":"Histopathology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1746-1596-5-37","article-title":"Thyroid transcription factor-1 positive primary breast cancer: A case report with review of the literature","volume":"5","author":"Klingen","year":"2010","journal-title":"Diagn. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1097\/PAS.0b013e3181f884e8","article-title":"Thyroid Transcription Factor-1 Expression in Breast Carcinomas","volume":"34","author":"Robens","year":"2010","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1309\/4WV79N2GHJ3X1841","article-title":"Immunohistochemistry of Estrogen and Progesterone Receptors Reconsidered","volume":"123","author":"Nadji","year":"2005","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1097\/PAI.0b013e3181bec23b","article-title":"Immunohistochemical Expression of Estrogen Receptor in Adenocarcinomas of the Lung","volume":"18","author":"Mejias","year":"2010","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1097\/JTO.0b013e3182904dfb","article-title":"Specificities of Lung Adenocarcinoma in Women Who Have Never Smoked","volume":"8","author":"Rouquette","year":"2013","journal-title":"J. Thorac. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"103","DOI":"10.4132\/jptm.2019.10.12","article-title":"Expression of female sex hormone receptors and its relation to clinicopathological characteristics and prognosis of lung adenocarcinoma","volume":"54","author":"Lee","year":"2020","journal-title":"J. Pathol. Transl. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.jtcvs.2005.06.012","article-title":"The significance of estrogen receptor \u03b2 in 301 surgically treated non\u2013small cell lung cancers","volume":"130","author":"Wu","year":"2005","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/s41568-019-0179-8","article-title":"Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy","volume":"19","author":"Skoulidis","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"R35","DOI":"10.1186\/bcr2857","article-title":"Mutations in the epidermal growth factor receptor (EGFR) gene in triple negative breast cancer: Possible implications for targeted therapy","volume":"13","author":"Teng","year":"2011","journal-title":"Breast Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1097\/PAI.0000000000000127","article-title":"Immunohistochemical Localization of Wild-type EGFR, E746-A750 Frame Deletion in Exon 19, and L858R Point Mutation in Exon 21 in Triple-negative Breast Cancer","volume":"23","author":"Vora","year":"2015","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1002\/cncr.22835","article-title":"Metastases to the breast from nonbreast solid neoplasms","volume":"110","author":"Williams","year":"2007","journal-title":"Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.gyobfe.2007.01.030","article-title":"Cancer du sein secondaire apr\u00e8s traitement pour maladie de Hodgkin. \u00c0 propos de sept cas","volume":"35","author":"Slimene","year":"2007","journal-title":"Gyn\u00e9cologie Obs. Fertil."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/modpathol.2012.191","article-title":"Non-mammary metastases to the breast and axilla: A study of 85 cases","volume":"26","author":"DeLair","year":"2013","journal-title":"Mod. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"482","DOI":"10.21037\/jtd.2017.12.61","article-title":"Influence of estrogen in non-small cell lung cancer and its clinical implications","volume":"10","author":"Arrieta","year":"2018","journal-title":"J. Thorac. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/nrc2190","article-title":"Lung cancer in never smokers\u2014A different disease","volume":"7","author":"Sun","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1200\/JCO.2008.18.3251","article-title":"Association Between Estrogen Receptor-\u03b2 Expression and Epidermal Growth Factor Receptor Mutation in the Postoperative Prognosis of Adenocarcinoma of the Lung","volume":"27","author":"Nose","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.steroids.2006.11.019","article-title":"Estrogen receptor signaling pathways in human non-small cell lung cancer","volume":"72","author":"Chen","year":"2007","journal-title":"Steroids"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.biopha.2012.02.004","article-title":"Combine therapy of gefitinib and fulvestrant enhances antitumor effects on NSCLC cell lines with acquired resistance to gefitinib","volume":"66","author":"Xu","year":"2012","journal-title":"Biomed. Pharmacother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.lungcan.2018.06.013","article-title":"Randomized phase II study of fulvestrant and erlotinib compared with erlotinib alone in patients with advanced or metastatic non-small cell lung cancer","volume":"123","author":"Garon","year":"2018","journal-title":"Lung Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3172","DOI":"10.1158\/1078-0432.CCR-19-3056","article-title":"Randomized Phase II Trial Evaluating Treatment with EGFR-TKI Associated with Antiestrogen in Women with Nonsquamous Advanced-Stage NSCLC: IFCT-1003 LADIE Trial","volume":"26","author":"Mazieres","year":"2020","journal-title":"Clin. Cancer Res."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/28\/5\/292\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:53:19Z","timestamp":1760165599000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/28\/5\/292"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,31]]},"references-count":50,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["curroncol28050292"],"URL":"https:\/\/doi.org\/10.3390\/curroncol28050292","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,31]]}}}