Stratification of Tamoxifen Synergistic Combinations for the Treatment of ER+ Breast Cancer.
Emily K Zboril, Jacqueline M Grible, David C Boyd, Nicole S Hairr, Tess J Leftwich, Madelyn F Esquivel, Alex K Duong, Scott A Turner, Andrea Ferreira-Gonzalez, Amy L Olex, Carol A Sartorius, Mikhail G Dozmorov, J Chuck Harrell
Author Information
Emily K Zboril: Department of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Jacqueline M Grible: Department of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.
David C Boyd: Department of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Nicole S Hairr: Department of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA. ORCID
Tess J Leftwich: Department of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Madelyn F Esquivel: Department of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA. ORCID
Alex K Duong: Department of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA. ORCID
Scott A Turner: Department of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Andrea Ferreira-Gonzalez: Department of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Amy L Olex: C. Kenneth and Dianne Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA 23298, USA. ORCID
Carol A Sartorius: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Mikhail G Dozmorov: Department of Biostatistics, Virginia Commonwealth University, Richmond, VA 23298, USA. ORCID
J Chuck Harrell: Department of Pathology, Virginia Commonwealth University, Richmond, VA 23298, USA. ORCID
Breast cancer alone accounts for the majority of cancer deaths among women, with the most commonly diagnosed subtype being estrogen receptor positive (ER+). Survival has greatly improved for patients with ER+ breast cancer, due in part to the development of antiestrogen compounds, such as tamoxifen. While treatment of the primary disease is often successful, as many as 30% of patients will experience recurrence and metastasis, mainly due to developed endocrine therapy resistance. In this study, we discovered two tamoxifen combination therapies, with simeprevir and VX-680, that reduce the tumor burden in animal models of ER+ breast cancer more than either compound or tamoxifen alone. Additionally, these tamoxifen combinations reduced the expression of HER2, a hallmark of tamoxifen treatment, which can facilitate acquisition of a treatment-resistant phenotype. These combinations could provide clinical benefit by potentiating tamoxifen treatment in ER+ breast cancer.
