Journal article
Targeting Estrogen Receptor Beta in a Phase 2 Study of High-Dose Estradiol in Metastatic Triple-Negative Breast Cancer: A Wisconsin Oncology Network Study
Clinical breast cancer, Vol.16(4), pp.256-261
08/2016
DOI: 10.1016/j.clbc.2016.03.005
PMCID: PMC4969205
PMID: 27133732
Abstract
Estrogen receptor beta (ERβ) is a potential therapeutic target in triple-negative breast cancer (TNBC). This 2-stage phase 2 study investigated estradiol in advanced TNBC. The study was closed after 17 patients completed the first stage. One patient with an ERβ-positive tumor experienced a prolonged confirmed partial response. Future study of ERβ agonists in selected TNBC may be warranted.
Estrogen receptor beta (ERβ) is expressed by 50% to 80% of triple-negative breast cancers (TNBC). Agonism of ERβ has antiproliferative effects in TNBC cells expressing ERβ. This phase 2 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 3 times daily provided continuously for 28-day cycles. A Simon optimal 2-stage design was used. The primary end point was objective response (OR). Secondary end points 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 years (range, 34-90 years); the median number of prior systemic therapies was 2 (range, 0-6). One patient had a confirmed partial response (OR rate, 5.9%) and remained on the study for > 24 weeks. Three patients had stable disease, with 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 as a result of 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.
Details
- Title: Subtitle
- Targeting Estrogen Receptor Beta in a Phase 2 Study of High-Dose Estradiol in Metastatic Triple-Negative Breast Cancer: A Wisconsin Oncology Network Study
- Creators
- Kari B. Wisinski - University of Wisconsin–MadisonWei Xu - University of Wisconsin–MadisonAmye J. Tevaarwerk - University of Wisconsin–MadisonSandeep Saha - University of Wisconsin–MadisonKyungMann Kim - University of Wisconsin–MadisonAnne Traynor - University of Wisconsin–MadisonLeah Dietrich - Gundersen Lutheran Health System, Lacrosse, WIRobert Hegeman - University of Wisconsin–MadisonDhimant Patel - Vince Lombardi Cancer Clinic, Aurora HealthCare Network, Green Bay, WIJules Blank - Saint Vincent Health SystemJosephine Harter - University of Wisconsin–MadisonMark E. Burkard - University of Wisconsin–Madison
- Resource Type
- Journal article
- Publication Details
- Clinical breast cancer, Vol.16(4), pp.256-261
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.clbc.2016.03.005
- PMID
- 27133732
- PMCID
- PMC4969205
- ISSN
- 1526-8209
- eISSN
- 1938-0666
- Number of pages
- 6
- Language
- English
- Date published
- 08/2016
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984701256102771
Metrics
5 Record Views