{"_buckets": {"deposit": "c812b250-56ae-4d52-83a6-f5af5891a14a"}, "_deposit": {"id": "53590", "owners": [], "pid": {"revision_id": 0, "type": "depid", "value": "53590"}, "status": "published"}, "_oai": {"id": "oai:tsukuba.repo.nii.ac.jp:00053590"}, "item_5_biblio_info_6": {"attribute_name": "\u66f8\u8a8c\u60c5\u5831", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2019-09", "bibliographicIssueDateType": "Issued"}, "bibliographicIssueNumber": "5", "bibliographicPageEnd": "543", "bibliographicPageStart": "535", "bibliographicVolumeNumber": "26", "bibliographic_titles": [{"bibliographic_title": "Breast cancer"}]}]}, "item_5_description_4": {"attribute_name": "\u6284\u9332", "attribute_value_mlt": [{"subitem_description": "Background\nAn association between CYP2D6 polymorphisms and tamoxifen (TAM) efficacy has not been confirmed, partly due to unreliable prediction of active metabolite exposure solely by CYP2D6 activity. The efficacy of TAM dose escalation appears limited in poor TAM metabolizers. Since the chlorine atom on the side chain of toremifene (TOR) prevents 4-hydroxylation by CYP2D6, its contribution to active conversion of TOR is minor. We examined the role of TOR and its dose escalation among poor TAM metabolizers.\n\nMethods\nThe pharmacokinetics (PK) and pharmacogenomics (PGx) of TAM and TOR were studied. Correlation between PK and CYP2D6 inhibitor use, smoking status, and PGx were examined by regression analysis. For patients showing low endoxifen levels, an intra-patient dose escalation of TOR was conducted, and TOR was increased from 40 to 120 mg for \u2265\u200924 weeks with PK sampling. Total activity was calculated as the sum of the concentration of each active metabolite adjusted by their respective in vitro activities.\n\nResults\nFifty and 11 of the 273 participating patients had endoxifen levels\u2009\u003c\u200915 and \u003c\u20097.5 ng/mL, respectively. The CYP2D6 genotype was the major determinant for TAM activity (p\u2009\u003c\u20090.01). Smoking status (p\u2009=\u20090.07) and the CYP2C19 phenotype (p\u2009=\u20090.07), but not the CYP2D6 genotype (p\u2009=\u20090.61), showed marginally significant effects on TOR activity. TOR activity increased significantly with dose escalation, even among poor TAM metabolizers, and was maintained for \u2265\u200924 weeks.\n\nConclusion\nTOR might be a valid alternative to TAM in patients predicted to be poor TAM metabolizers.", "subitem_description_type": "Abstract"}]}, "item_5_publisher_27": {"attribute_name": "\u51fa\u7248\u8005", "attribute_value_mlt": [{"subitem_publisher": "Springer"}]}, "item_5_relation_10": {"attribute_name": "PubMed\u756a\u53f7", "attribute_value_mlt": [{"subitem_relation_type_id": {"subitem_relation_type_id_text": "30734152", "subitem_relation_type_select": "PMID"}}]}, "item_5_relation_11": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_type_id": {"subitem_relation_type_id_text": "10.1007/s12282-019-00952-9", "subitem_relation_type_select": "DOI"}}]}, "item_5_rights_12": {"attribute_name": "\u6a29\u5229", "attribute_value_mlt": [{"subitem_rights": "\u00a9 The Author(s) 2019"}, {"subitem_rights": "This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made."}]}, "item_5_select_15": {"attribute_name": "\u8457\u8005\u7248\u30d5\u30e9\u30b0", "attribute_value_mlt": [{"subitem_select_item": "publisher"}]}, "item_5_source_id_7": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "1340-6868", "subitem_source_identifier_type": "ISSN"}]}, "item_5_source_id_9": {"attribute_name": "\u66f8\u8a8c\u30ec\u30b3\u30fc\u30c9ID", "attribute_value_mlt": [{"subitem_source_identifier": "AA1103354X", "subitem_source_identifier_type": "NCID"}]}, "item_creator": {"attribute_name": "\u8457\u8005", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "\u5742\u6771, \u88d5\u5b50"}, {"creatorName": "\u30d0\u30f3\u30c9\u30a6, \u30d2\u30ed\u30b3", "creatorNameLang": "ja-Kana"}, {"creatorName": "BANDO, Hiroko", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "741", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "00400680", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://nrid.nii.ac.jp/ja/nrid/1000000400680"}, {"nameIdentifier": "0000002296", "nameIdentifierScheme": "\u7b51\u6ce2\u5927\u5b66\u7814\u7a76\u8005\u7dcf\u89a7", "nameIdentifierURI": "http://trios.tsukuba.ac.jp/researcher/0000002296"}]}, {"creatorNames": [{"creatorName": "Ishiguro, Hiroshi", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "216565", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Ohno, Shinji", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "216566", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Yamamoto, Yutaka", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "216567", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Takao, Shintaro", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "216568", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Sato, Nobuaki", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "216569", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Fujisawa, Tomomi", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "216570", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kadoya, Takayuki", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "216571", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kuroi, Katsumasa", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "216572", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Teramura, Yasufumi", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "216573", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Iwata, Hiroji", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "216574", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Tanaka, Shiro", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "216575", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Toi, Masakazu", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "216576", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "\u30d5\u30a1\u30a4\u30eb\u60c5\u5831", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2019-11-28"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "BC_26-5.pdf", "filesize": [{"value": "848.0 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_6", "mimetype": "application/pdf", "size": 848000.0, "url": {"label": "BC_26-5", "url": "https://tsukuba.repo.nii.ac.jp/record/53590/files/BC_26-5.pdf"}, "version_id": "c68c6475-b0f7-4a97-9a47-dc0002d88308"}]}, "item_language": {"attribute_name": "\u8a00\u8a9e", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "\u8cc7\u6e90\u30bf\u30a4\u30d7", "attribute_value_mlt": [{"resourcetype": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "Pharmacogenomic\u2013pharmacokinetic study of selective estrogen-receptor modulators with intra-patient dose escalation in breast cancer", "item_titles": {"attribute_name": "\u30bf\u30a4\u30c8\u30eb", "attribute_value_mlt": [{"subitem_title": "Pharmacogenomic\u2013pharmacokinetic study of selective estrogen-receptor modulators with intra-patient dose escalation in breast cancer"}]}, "item_type_id": "5", "owner": "1", "path": ["2780/2176", "3/62/5297/2013"], "permalink_uri": "http://hdl.handle.net/2241/00159008", "pubdate": {"attribute_name": "\u516c\u958b\u65e5", "attribute_value": "2019-11-28"}, "publish_date": "2019-11-28", "publish_status": "0", "recid": "53590", "relation": {}, "relation_version_is_last": true, "title": ["Pharmacogenomic\u2013pharmacokinetic study of selective estrogen-receptor modulators with intra-patient dose escalation in breast cancer"], "weko_shared_id": 5}