Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Oncodesign, Dijon, France.
Anticancer Res. 2020 Dec;40(12):6699-6712. doi: 10.21873/anticanres.14693.
BACKGROUND/AIM: There is no established standard chemotherapy after administration of the combination endocrine plus CDK4/6 inhibitor therapy for luminal-type breast cancer. We used patient-derived xenograft (PDX) models to determine the antitumor activity of eribulin and capecitabine after endocrine therapy plus CDK4/6 inhibitor.
We examined the antitumor activity of fulvestrant, palbociclib, eribulin, and capecitabine in 4 luminal-type breast cancer PDX models (OD-BRE-0188, -0438, -0450, -0745). In OD-BRE-0438, we determined the antitumor activity of chemotherapy after fulvestrant-palbociclib treatment. We also performed immunohistochemical analysis to explore the effects of treatment on E-cadherin in tumor tissues.
Fulvestrant, fulvestrant-palbociclib and chemotherapy had antitumor activity in the 4 PDX models. In OD-BRE-0438 (the most resistant to fulvestrant-palbociclib), eribulin had superior antitumor activity to capecitabine after fulvestrant plus palbociclib. Only eribulin tended to increase E-cadherin expression.
Eribulin had superior antitumor activity to capecitabine after fulvestrant-palbociclib in the OD-BRE-0438 model.
背景/目的：激素受体阳性（HR+）、人表皮生长因子受体 2 阴性（HER2-）型乳腺癌接受内分泌联合 CDK4/6 抑制剂治疗后，尚未确立标准的化疗方案。本研究旨在使用患者来源的异种移植（PDX）模型，评估内分泌联合 CDK4/6 抑制剂治疗后，艾瑞布林和卡培他滨的抗肿瘤活性。
我们在 4 例 HR+/HER2-型乳腺癌 PDX 模型（OD-BRE-0188、-0438、-0450、-0745）中，检测氟维司群、哌柏西利、艾瑞布林和卡培他滨的抗肿瘤活性。在 OD-BRE-0438 模型中，我们评估了氟维司群-哌柏西利治疗后的化疗抗肿瘤活性，并进行了免疫组化分析以探讨治疗对肿瘤组织中 E-钙黏蛋白的影响。
氟维司群、氟维司群-哌柏西利和化疗在 4 例 PDX 模型中均具有抗肿瘤活性。在氟维司群-哌柏西利治疗耐药性最强的 OD-BRE-0438 模型中，艾瑞布林的抗肿瘤活性优于卡培他滨。仅艾瑞布林有增加 E-钙黏蛋白表达的趋势。
在 OD-BRE-0438 模型中，氟维司群-哌柏西利治疗后，艾瑞布林的抗肿瘤活性优于卡培他滨。
