Abstract
Background: Targeting growth factor and survival pathways may delay endocrine-resistance in estrogen receptor-positive breast cancer.
Materials & methods: A pilot Phase II study adding sorafenib to endocrine therapy in 11 patients with metastatic estrogen receptor-positive breast cancer was conducted. Primary end point was response by RECIST after 3 months of sorafenib. Secondary end points included safety, time to progression and biomarker modulation. The study closed early owing to slow accrual.
Results: Eight out of 11 patients had progressive disease on study entry and three had stable disease. Of the ten evaluable patients, seven experienced stable disease (70%) and three experienced progressive diseas (30%), with a median time to progression of 6.1 months (8.4 months in the seven patients on tamoxifen). The serum samples demonstrated a significant reduction in VEGF receptor 2 and PDGF receptor-α. Microarray analysis identified 32 suppressed genes, no induced genes and 29 enriched Kyoto Encyclopedia of Genes and Genomes pathways.
Conclusion: The strategy of adding a targeted agent to endocrine therapy upon resistance may be worthwhile testing in larger studies.
| Original language | English |
|---|---|
| Pages (from-to) | 2435-2448 |
| Number of pages | 14 |
| Journal | Future Oncology |
| Volume | 10 |
| Issue number | 15 |
| DOIs | |
| State | Published - Dec 1 2014 |
Bibliographical note
Publisher Copyright:© 2014 Future Medicine Ltd.
Funding
| Funders | Funder number |
|---|---|
| National Center for Research Resources | UL1RR033173, TL1 RR033172, KL2 RR033171 |
| National Institutes of Health (NIH) | |
| National Childhood Cancer Registry – National Cancer Institute | P30CA177558 |
Keywords
- PDGF receptor-α
- Ras/Raf/MAPK
- VEGF receptor 2
- angiogenesis
- breast cancer
- endocrine resistance
ASJC Scopus subject areas
- Oncology
- Cancer Research
