Vitamin D and Androgen Receptor-Targeted Therapy Are Effective in Triple-Negative Breast Cancer

Vitamin D and androgen receptor-targeted therapy successfully reduced growth and induced death of cancerous cells in a cell culture model of triple-negative breast cancer (TNBC). This could offer a treatment option beyond chemotherapy for patients with TNBC, which is an aggressive type of breast cancer that is usually unresponsive to hormone receptor-targeted treatments.

"The most successful treatments for breast cancer target hormone receptors; if you remove the hormone or block it, the cancer cells are less likely to survive," said Tan A. Ince, MD, PhD, breast cancer pathologist at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, Miami, Florida, and lead author of the study.

"However, triple-negative tumors have been unresponsive to receptor-targeted treatments. It was only when we discovered that two-thirds of triple-negative breast cancers express vitamin D and androgen receptors that we were able to treat the tumors using a hormone-receptor approach."

Breast cancers are either hormone-receptor positive or hormone-receptor negative. When the disease is hormone-receptor positive, then hormone-receptor treatment can effectively treat the disease by blocking the hormones that contribute to growth of the disease.

As TNBC cells lack hormone receptors for estrogen, progesterone, and human epidermal growth factor receptor 2, hormone-receptor therapy cannot treat TNBC. The prognosis for patients with TNBC is usually worse than the prognosis for patients with other types of breast cancer.

This study found that TNBC cells do express androgen receptors and vitamin D receptors. The researchers co-targeted androgen receptors and vitamin D receptors with agonist hormones, revealing a reduction in the growth and sustainability of the cancerous cells. This discovery could result in the use of targeted receptor therapy to treat TNBC, which might result in improved prognoses.

This treatment also inhibited cancer stem cells.

"There is growing evidence that breast cancer consists of different subtypes of cells including noncancer stem cells and cancer stem cells," said Ince.

"These stem cells possess the ability to self-renew and are thought to be associated with resistance to standard therapies as well as with metastasis. Targeting cancer stem cells may be important for complete tumor remission."

The greatest reduction in growth of cancerous cells occurred when androgen receptor-targeted and vitamin D receptor-targeted therapies were combined with chemotherapy.

Reference

1. Thakkar A, Wang B, Picon-Ruiz M, Buchwald P, Ince TA. Vitamin D and androgen receptor-targeted therapy for triple-negative breast cancer [published online April 27, 2016]. Breast Cancer Res Treat. doi:10.1007/s10549-016-3807-y.

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