Stratification of Tamoxifen Synergistic Combinations for the Treatment of ER+ Breast Cancer

Stratification of Tamoxifen Synergistic Combinations for the Treatment of ER+ Breast Cancer

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....

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Bibliographic Details
Published in:Cancers Vol. 15; no. 12; p. 3179
Main Authors: Zboril, Emily K, Grible, Jacqueline M, Boyd, David C, Hairr, Nicole S, Leftwich, Tess J, Esquivel, Madelyn F, Duong, Alex K, Turner, Scott A, Ferreira-Gonzalez, Andrea, Olex, Amy L, Sartorius, Carol A, Dozmorov, Mikhail G, Harrell, J Chuck
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 14-06-2023
MDPI
Subjects:
Analysis
Animal models
Antiestrogens
Antimitotic agents
Antineoplastic agents
Breast cancer
Cancer therapies
Drug therapy, Combination
Endocrine therapy
ErbB-2 protein
Estrogen
Estrogen receptors
Estrogens
Genomes
Metastases
Ovarian cancer
Patients
Penicillin
Phenotypes
Prognosis
Quality control
Survival
Tamoxifen
Tumors
Womens health
St Louis Missouri
United States > US
ER+ breast cancer
drug synergism
endocrine resistance
estrogen receptor
patient-derived xenograft
tamoxifen
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Summary: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.
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ISSN:2072-6694
2072-6694
DOI:10.3390/cancers15123179