Nuclear receptors are key proteins that regulate cell proliferation, death, and differentiation. In breast cells, estrogen receptors (ERs) are critical for mammary gland development, differentiation, and tumorigenesis, and selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene, and aromatase inhibitors can prevent the development of ER-positive breast cancer. Other nuclear transcription factors are critical regulators of proliferation and differentiation including retinoic acid receptors (RARs), vitamin D receptors (VDR), and peroxisome proliferator-activator receptors (PPARs). Each of these ligand activated nuclear hormone receptors bind the retinoid X receptors (RXRs) to regulate gene expression. Ligands of these nuclear hormone receptors have been shown to prevent many different types of cancer, including breast cancer. I will present results in preclinical and early clinical studies testing retinoids, rexinoids, Vitamin D analogs, and PPAR ligands for the prevention of breast cancer. Our results and the results of others have shown that ligands that bind and activate the rexinoid receptor are highly effective in preventing breast cancer in animals, particularly ER-negative breast cancer. These preclinical results supported the testing of the RXR ligand bexarotene in women at high risk of breast cancer. This early study demonstrated a biological effect of bexarotene on breast tissue in women. We and other have conducted preclinical studies testing combinations of nuclear hormone receptor ligands (RXR ligand + anti-estrogen SERMS)(RXR ligand + Vitamin D analog) and (RXR ligand + PPAR agonist). These results demonstrate that nuclear hormone receptor ligands can be used to prevent breast cancer and that rexinoids and other ligands provide an opportunity to prevent all forms of breast cancer.

Supported by RO1CA078480-11

Citation Format: Abhijit Mazumdar, Ivan Uray, Beate Litzenburger, Yun Zhang, Jamal Hill, Nanjoo Suh, Powel Brown. Targeting nuclear hormone receptors for breast cancer prevention. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr ED05-01.

©2013 American Association for Cancer Research.
2013