image: Androgen (AR, in red) and vitamin D (VDR, in green) receptors are present in the nuclei of a subset of breast cells (yellow). view more
Credit: Sylvester Comprehensive Cancer Center
MIAMI, May 23, 2016 - A recent study by researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine revealed that triple-negative breast cancer (TNBC), which has generally been unresponsive to hormone receptor-targeted treatments, can indeed be treated using vitamin D and androgen receptor-targeted therapy. The discovery offers a new treatment option beyond chemotherapy for this aggressive type of breast cancer. The study was published in the journal Breast Cancer Research and Treatment.
"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, M.D., Ph.D., breast cancer pathologist at Sylvester 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."
Hormone-receptor positive vs. negative breast cancer
Breast cancers can be categorized into two subtypes - those which are hormone-receptor positive and hormone-receptor negative. For hormone-receptor positive cancer cells, hormone-receptor therapy can be used to interrupt the role of hormones in the cells' growth and overall function. Due to the lack of receptors, this type of therapy was not an option for TNBC. Additionally, the prognosis for patients with TNBC is usually poorer than for those with other types of breast cancers.
Ince and his team found that although TNBC lacks the three receptors that fuel most breast cancers - estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 - it does express androgen receptors (AR) and vitamin D receptors (VDR). This provided the basis for the study. The researchers showed that co-targeting AP and VDR with agonist hormones turned out to be an effective strategy to reduce the sustainability of the cancer cells. This could lead to the use of targeted receptor therapy in the treatment of TNBC and, in turn, to better patient outcomes.
Breast cancer stem cells
"There is growing evidence that breast cancer consists of different subtypes of cells including non-cancer stem cells and cancer stem cells," said Ince, who is also associate professor of pathology at the University of Miami Miller School of Medicine. "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 research offers new options to treat TNBC and insights into the role of stem cells in the spread of cancer. While hormone-receptor therapy plays an important role in treating TNBC, a combined approach with chemotherapy yielded the best results.
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This study was supported by funding from the Breast Cancer Research Foundation and Play for P.I.N.K., NIEHS R01-ES024991 and NCI R01-CA146445 from the NIH Roadmap Epigenomics Project, as well as from Sylvester Comprehensive Cancer Center's Women's Cancer Association.
About Sylvester Comprehensive Cancer Center
Sylvester Comprehensive Cancer Center, part of UHealth - the University of Miami Health System and the University of Miami Miller School of Medicine, is among the nation's leading cancer centers and South Florida's only Cancer Center of Excellence. A 2015 study by Memorial Sloan Kettering Cancer Center, published in The Journal of the American Medical Association, showed that cancer patients treated at Sylvester have a 10 percent higher chance of survival than those treated at nearly any other cancer center in the nation. With the combined strength of more than 120 cancer researchers and 130 cancer specialists, Sylvester discovers, develops and delivers more targeted therapies, providing the next generation of cancer clinical care - precision cancer medicine - to each patient. Our comprehensive diagnostics, coupled with teams of scientific and clinical experts who specialize in just one type of cancer, enable us to better understand each patient's individual cancer and develop treatments that target the cells and genes driving the cancer's growth and survival, leading to better outcomes. At Sylvester, patients have access to more treatment options and more cancer clinical trials than most hospitals in the southeastern United States. To better serve current and future patients, Sylvester has a network of conveniently located outpatient treatment facilities in Miami, Kendall, Hollywood, Plantation, Deerfield Beach and Coral Springs, with plans to open in Coral Gables in 2016. For more information, visit sylvester.org.
Journal
Breast Cancer Research and Treatment