Androgen and vitamin D receptors can be targeted in breast cancer, according to new research. Although estrogen receptors are commonly targeted in breast cancer that is hormone-dependent, this research offers the possibility of expanding the ways that patients with breast cancer are treated with hormone therapy.
“These findings may change how we treat breast cancer,” said Sandro Santagata, MD, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts. “Since at least 50% of patients with breast cancer express all three receptors—estrogen, androgen, and vitamin D in their tumor cells, this may allow clinicians to consider triple hormone treatments, which is a new concept, as opposed to treating patients by targeting only estrogen receptors.”
The study was published online in the Journal of Clinical Investigation (2014; doi:10.1172/JCI70941).
When clinicians categorize human breast cancer tumors, they do so by grouping them into one of three categories based on the type of receptor present or absent on the tumor: estrogen receptor (ER)- positive/negative, progesterone receptor (PR)-positive/negative), and human epidermal growth factor receptor 2 (HER2)-positive/negative.
In this study, the researchers explored the landscape of cells that make up the surfaces of breast tissue to provide a better definition of the subtypes of cells present on these surfaces. They studied more than 15,000 normal breast cells and discovered 11 previously undefined cell subtypes. Interestingly, these 11 normal breast cell types were categorized into four new hormonal differentiation groups (HR 0, 1, 2, 3), which were characterized by vitamin D, androgen, and estrogen hormone receptor expression.
The researchers took this information and compared it against 3,157 human breast tumors of patients and found that the patients’ tumor make-up was similar to one of the 11 normal cell types they discovered. Moreover, the patients had different survival rates and responses to hormone treatments depending on whether the cell types were in the HR 0, 1, 2, or 3 subgroup.
According to the researchers, the HR categories may be helpful in refining classifications presently used to classify breast cancers. Moreover, the findings open the door to the option of triple-hormone treatments, which may be more effective than single-hormone treatments and may help patients who are resistant to anti-estrogen treatments.
“There are many other interesting treatment opportunities that our findings may lead to,” said Santagata. “For instance, early data suggest that targeting androgen and vitamin D receptors in addition to standard chemotherapy may increase effectiveness, and may allow for lower doses of chemotherapy with the same effect.”
Also, Santagata explained that these results may be important for triple-negative breast carcinomas, which cannot be treated with conventional endocrine-targeted therapies. The study results suggest that two-thirds of these patients may be candidates for androgen and vitamin D-targeted hormone therapy. Perhaps equally important, researchers found that some breast tumor subtypes, such as basal-like carcinoma, have been classified erroneously due to inaccurate taxonomy of normal cell types.