Targeting Estrogen Receptor Beta in a Phase 2 Study of High-Dose Estradiol in Metastatic Triple-Negative Breast Cancer: A Wisconsin Oncology Network Study.
Targeting Estrogen Receptor Beta in a Phase 2 Study of High-Dose Estradiol in Metastatic Triple-Negative Breast Cancer: A Wisconsin Oncology Network Study.
复制标题
DOI：
10.1016/j.clbc.2016.03.005
复制
发表时间：
2016-08
影响因子：
3.1
通讯作者：
Burkard ME
中科院分区：
文献类型：
--
作者：
Wisinski KB;Xu W;Tevaarwerk AJ;Saha S;Kim K;Traynor A;Dietrich L;Hegeman R;Patel D;Blank J;Harter J;Burkard ME
Estrogen receptor beta (ERβ) is expressed by 50-80% of triple negative breast cancers (TNBC). Agonism of ERβ has antiproliferative effects in TNBC cells expressing ERβ. This phase II study evaluated single agent high dose estradiol in patients with advanced TNBC. Adult women with measurable advanced TNBC were treated with estradiol 10 mg oral three times daily given continuously for 28-day cycles. A Simon optimal two-stage design was used. The primary endpoint was objective response (OR). Secondary endpoints included progression-free survival (PFS), clinical benefit (CB), and safety. OR, CB and PFS by ERβ status were also examined. Seventeen evaluable women were enrolled. Median age was 58 (34-90); the median number of prior systemic therapies was 2 (0-6). One patient had a confirmed partial response (OR rate of 5.9%) and remained on study for >24 weeks. Three patients had stable disease, one lasting more than 16 weeks. ERβ expression was detected in 77% (13 patients). The CB rate at 16 weeks was 15% (2 of 13) in ERβ positive patients and 0% (0 of 4) in ERβ negative patients (p= 1). PFS was poor (median 1.9 months) and not statistically significantly different between ERβ-positive versus negative patients. No new adverse events from estradiol were identified. The study closed after the first stage due to limited responses in these unselected patients. In unselected TNBC, high dose estradiol has limited efficacy. However, further evaluation of ERβ selective agonists in TNBC selected by ERβ expression may be warranted.
