{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:15:48Z","timestamp":1792782948822,"version":"4.5.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"This work was supported by Astellas Pharma Inc. and Pfizer Inc., the co-developers of enzalutamide (no grant number is applicable)."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer Res Treat"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      Androgen receptor (AR) expression occurs in up to 86% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers. In vitro\n                      <jats:italic>,<\/jats:italic>\n                      AR inhibitors enhance antitumor activity of trastuzumab, an anti-HER2 antibody, in trastuzumab-resistant HER2+\u2009cell lines. This open-label, single-arm, phase II study evaluated the efficacy and safety of enzalutamide, an AR-signaling inhibitor, in patients with advanced HER2+\u2009AR+\u2009breast cancer previously treated with trastuzumab.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eligible patients had measurable or non-measurable evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Eastern Cooperative Oncology Group status\u2009\u2264\u20091, no history of brain metastases, and previously received\u2009\u2265\u20091 anti-HER2 regimen for advanced disease. Patients received 160\u00a0mg oral enzalutamide daily and 6\u00a0mg\/kg intravenous trastuzumab every 21\u00a0days until disease progression or unacceptable toxicity. Primary end point was clinical benefit rate at 24\u00a0weeks (CBR24); secondary end points included progression-free survival (PFS) and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall, 103\u00a0women were enrolled [median age 60\u00a0years (range\u200934\u201383)]; 62% had received\u2009\u2265\u20093\u00a0lines of prior anti-HER2 therapy. CBR24, comprising patients with confirmed partial responses (5%) and durable stable disease at 24\u00a0weeks (19%), was 24% in the efficacy evaluable set (\n                      <jats:italic>n\u2009<\/jats:italic>\n                      =\u200989). CBR24 did not seem related to AR-expression levels or hormone receptor status. Median PFS was 3.4\u00a0months (95% confidence interval 2.0\u20133.8). Overall, 97 (94%) patients experienced treatment-emergent adverse events (TEAEs), with fatigue most common (34%). Dyspnea (4%) and malignant neoplasm progression (3%) were the only TEAEs grade\u2009\u2265\u20093 reported in\u2009\u2265\u20093\u00a0patients. 22 patients (21%) reported serious TEAEs. Four patients (4%) experienced fatal, non-drug-related TEAEs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Enzalutamide plus trastuzumab was well tolerated, and a subset of patients in this heavily pretreated population had durable disease control. Determination of biomarkers is needed to identify patients most likely to benefit from this combination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>ClinicalTrials.gov number<\/jats:title>\n                    <jats:p>NCT02091960<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10549-021-06109-7","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T20:06:13Z","timestamp":1613678773000},"page":"155-165","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["The efficacy and safety of enzalutamide with trastuzumab in patients with HER2+\u2009and androgen receptor-positive metastatic or locally advanced breast cancer"],"prefix":"10.1007","volume":"187","author":[{"given":"Andrew","family":"Wardley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Cortes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Provencher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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JC reports a role as study investigator with Astellas during the conduct of this study and consulting\/advisory roles with AstraZeneca, Biothera, Celgene, Cellestia, Eisai, Novartis, Pfizer, and Roche outside the submitted work. LP reports a consulting\/advisory role with, and research funding from, Astellas and Medivation during the conduct of this study, a consulting\/advisory role with Lilly outside the submitted work, consulting\/advisory roles and research funding from Novartis, Pfizer, and Roche outside the submitted work and research funding from GlaxoSmithKline, Merck, and Odonate outside the submitted work. KM, AJC, ICT, MH, RY, RB, LH, SC, PG, PN, and SR report a role as study investigator with Astellas during the conduct of this study. HSR received research funding from Astellas during the conduct of this study. J Steinberg and J Sugg are full-time employees of Astellas. VA reports a role as study investigator with Astellas during the conduct of this study, research funding from Genentech outside the submitted work, and consulting\/advisory roles for AbbVie, Daiichi Sankyo, Eisai, and Novartis outside the submitted work. DC reports a role as study investigator with Astellas during the conduct of this study and consulting\/advisory roles for Novartis, Pfizer, Roche, and Syntheon outside the submitted work. GSW reports a consulting\/advisory role with, and research funding from, Astellas during the conduct of the study and research funding from AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Lilly, G1 Therapeutics, Genentech, Incyte, Janssen, MacroGenics, Medivation, Merrimack, Novartis, Pfizer, and Tesaro outside the submitted work and stock holdings from Puma and Roche outside the submitted work. M-PG reports a role as study investigator with Astellas during the conduct of this study and consulting\/advisory roles with Lilly, Novartis, Pfizer, and Roche outside the submitted work. IEK reports research funding from Pfizer during the conduct of the study, a consulting\/advisory role with Astellas during the conduct of this study, a consulting\/advisory role with, and research funding from, Genentech\/Roche outside the submitted work, and consulting\/advisory roles with Context, Daiichi Sankyo, MacroGenics, Novartis, and Taiho outside the submitted work.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}