Dr. Germain on Scientific Rationale Behind Bortezomib/Fulvestrant for HR+ Breast Cancer

Doris Germain, PhD, ‎associate professor at Mount Sinai Cancer Institute, discusses the scientific rationale behind a clinical trial comparing fulvestrant alone with bortezomib plus fulvestrant for the treatment of hormone receptor-positive metastatic breast cancer.

Fulvestrant promotes the aggregation of the newly synthesized estrogen-receptor (ER) in the cytoplasm, which leads to cell death. However, this effect is limited as a result of the proteasome.

By combining fulvestrant with the proteasome inhibitor, bortezomib, the fulvestrant-mediated aggregation is enhanced without blocking the degradation of the ER in the nucleus. This induces tumor regression. The impact of the bortezomib/fulvestrant combination was further investigated in a phase II clinical trial led by Kerin Adelson, MD.