High-Dose Toremifene as a Promising Candidate Therapy for Hormone Receptor-Positive Metastatic Breast Cancer with Secondary Resistance to Aromatase Inhibitors.

IF 1.6 Q4 ONCOLOGY
International Journal of Breast Cancer Pub Date : 2020-02-12 eCollection Date: 2020-01-01 DOI:10.1155/2020/7156574
Atsushi Fushimi, Isao Tabei, Azusa Fuke, Tomoyoshi Okamoto, Hiroshi Takeyama
{"title":"High-Dose Toremifene as a Promising Candidate Therapy for Hormone Receptor-Positive Metastatic Breast Cancer with Secondary Resistance to Aromatase Inhibitors.","authors":"Atsushi Fushimi,&nbsp;Isao Tabei,&nbsp;Azusa Fuke,&nbsp;Tomoyoshi Okamoto,&nbsp;Hiroshi Takeyama","doi":"10.1155/2020/7156574","DOIUrl":null,"url":null,"abstract":"<p><p>There are currently no established second- and later-line therapies for postmenopausal women with hormone receptor-positive advanced or metastatic breast cancer. We examined the efficacy of high-dose toremifene (HD-TOR) for this patient group and whether aromatase inhibitor (AI) resistance influences HD-TOR treatment outcome. This retrospective analysis investigated the outcomes of 19 women with postmenopausal hormone-sensitive recurrent or metastatic breast cancer who received HD-TOR, defined as 120 mg daily from 2012 to 2016. The median follow-up duration was 9.67 months. The overall response rate (ORR) and clinical benefit rate (CBR) were compared between various clinical subgroups, including patients exhibiting primary or secondary AI resistance as defined by the timing of recurrence or progression. Time to treatment failure (TTF) was estimated by the Kaplan-Meier method and compared between subgroups by the log-rank test. The overall ORR was 21.1%, and the CBR was 31.6%. CBR was significantly higher for patients without liver metastasis (50% vs. 0%, <i>p</i> = 0.044). Nine cases exhibited primary and eight cases secondary AI resistance. Both ORR and CBR were higher in patients with secondary AI resistance (25% vs. 0%, <i>p</i> = 0.087; 38% vs. 11%, <i>p</i> = 0.29). The median TTF was 6.2 months in the entire AI-resistant group (<i>n</i> = 17) and was longer in the secondary resistance subgroup than in the primary resistance subgroup (8.40 vs. 4.87 months; log-rank: <i>p</i> = 0.159). High-dose TOR appears to be most effective for postmenopausal breast cancer cases with secondary resistance to AIs, cases without prior AI treatment, and cases without liver metastasis. The detailed mechanisms of AI resistance and the clinical features of responsive cases need to be further clarified to identify the best candidates for HD-TOR.</p>","PeriodicalId":46159,"journal":{"name":"International Journal of Breast Cancer","volume":null,"pages":null},"PeriodicalIF":1.6000,"publicationDate":"2020-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/7156574","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Breast Cancer","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1155/2020/7156574","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/1/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 1

Abstract

There are currently no established second- and later-line therapies for postmenopausal women with hormone receptor-positive advanced or metastatic breast cancer. We examined the efficacy of high-dose toremifene (HD-TOR) for this patient group and whether aromatase inhibitor (AI) resistance influences HD-TOR treatment outcome. This retrospective analysis investigated the outcomes of 19 women with postmenopausal hormone-sensitive recurrent or metastatic breast cancer who received HD-TOR, defined as 120 mg daily from 2012 to 2016. The median follow-up duration was 9.67 months. The overall response rate (ORR) and clinical benefit rate (CBR) were compared between various clinical subgroups, including patients exhibiting primary or secondary AI resistance as defined by the timing of recurrence or progression. Time to treatment failure (TTF) was estimated by the Kaplan-Meier method and compared between subgroups by the log-rank test. The overall ORR was 21.1%, and the CBR was 31.6%. CBR was significantly higher for patients without liver metastasis (50% vs. 0%, p = 0.044). Nine cases exhibited primary and eight cases secondary AI resistance. Both ORR and CBR were higher in patients with secondary AI resistance (25% vs. 0%, p = 0.087; 38% vs. 11%, p = 0.29). The median TTF was 6.2 months in the entire AI-resistant group (n = 17) and was longer in the secondary resistance subgroup than in the primary resistance subgroup (8.40 vs. 4.87 months; log-rank: p = 0.159). High-dose TOR appears to be most effective for postmenopausal breast cancer cases with secondary resistance to AIs, cases without prior AI treatment, and cases without liver metastasis. The detailed mechanisms of AI resistance and the clinical features of responsive cases need to be further clarified to identify the best candidates for HD-TOR.

Abstract Image

Abstract Image

高剂量托瑞米芬作为激素受体阳性转移性乳腺癌对芳香酶抑制剂继发性耐药的有希望的候选疗法。
目前尚无针对绝经后女性激素受体阳性晚期或转移性乳腺癌的二线或二线治疗方法。我们检查了高剂量托瑞米芬(HD-TOR)对该患者组的疗效,以及芳香化酶抑制剂(AI)耐药性是否影响HD-TOR治疗结果。这项回顾性分析调查了19名绝经后激素敏感的复发或转移性乳腺癌妇女,她们在2012年至2016年期间接受了每天120毫克的HD-TOR治疗。中位随访时间为9.67个月。总缓解率(ORR)和临床获益率(CBR)在不同临床亚组之间进行比较,包括由复发或进展时间定义的原发性或继发性AI耐药患者。治疗失败时间(TTF)采用Kaplan-Meier法估计,亚组间采用log-rank检验比较。总ORR为21.1%,CBR为31.6%。无肝转移患者的CBR明显更高(50%比0%,p = 0.044)。原发性耐药9例,继发性耐药8例。继发性AI耐药患者的ORR和CBR均较高(25% vs 0%, p = 0.087;38% vs. 11%, p = 0.29)。整个ai耐药组(n = 17)的中位TTF为6.2个月,继发性耐药亚组比原发性耐药亚组更长(8.40个月比4.87个月;Log-rank: p = 0.159)。高剂量TOR似乎对绝经后对AI继发性耐药的乳腺癌患者、未接受过AI治疗的患者和无肝转移的患者最有效。需要进一步明确AI耐药的详细机制和反应病例的临床特征,以确定HD-TOR的最佳候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
3.40
自引率
0.00%
发文量
25
审稿时长
19 weeks
期刊介绍: International Journal of Breast Cancer is a peer-reviewed, Open Access journal that provides a forum for scientists, clinicians, and health care professionals working in breast cancer research and management. The journal publishes original research articles, review articles, and clinical studies related to molecular pathology, genomics, genetic predisposition, screening and diagnosis, disease markers, drug sensitivity and resistance, as well as novel therapies, with a specific focus on molecular targeted agents and immune therapies.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信