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October 15, 2015UAlbany Researcher Studying RNA-Based Tool to Decrease the Overtreatment of Breast Cancer
The difficulty in determining why some abnormal cells lead to life-threatening breast cancer and some do not has resulted in overdiagnosis and unnecessarily aggressive treatment, including mastectomy, for tens of thousands of women.
Now, an enigmatic RNA gene is being studied by a University at Albany Cancer Research Center (CRC) post-doctoral associate, Rebecca Sinnott DeVaux, as a tool to distinguish aggressive from indolent breast cancers and identify why some breast cancers become life-threatening metastasis. Her findings, she said, could greatly lessen the degree of overtreatment of breast cancer.
DeVaux’s study is the result of her winning a highly competitive “Breakthrough Award” from the U.S. Department of Defense’s Breast Cancer Research Program (she was one of 15 awarded from 321 proposals). The award is valued at just over a half-million dollars.
“The results of Dr. DeVaux’s cutting edge research will have an impact on the clinical care of breast cancer patients diagnosed with very early stage disease in the near future and on the treatment of more advanced breast cancer later on,” said Martin Tenniswood, CRC director and Empire Innovations Professor of biomedical sciences in the School of Public Health.
DeVaux noted that increased emphasis on breast cancer screening has led to a dramatic increase in diagnosis of pre-cancerous, or stage 0, ductal carcinoma in situ (DCIS) over the past 30 years. “Unfortunately, diagnosis of late stage invasive and metastatic disease has not proportionally declined,” she said. “This suggests that not all women diagnosed with DCIS would have developed a life threatening cancer. In fact, DCIS may never progress.”
Yet, because science does not currently understand what causes the progression to metastatic, life-threatening cancer, all women diagnosed with DCIS undergo an aggressive treatment strategy, including invasive lumpectomy or mastectomy coupled with radiation therapy.
DeVaux and her colleagues are using tumor biopsy samples from women who have both early stage DCIS and progressed, invasive breast cancer within the same breast. From these samples they have identified a group of genes called long noncoding RNAs (lncRNAs) that are enriched in the invasive samples. They are evaluating the role of the lncRNAs in driving breast cancer progression.
While the function of lncRNAs is largely unknown, they appear to be critical regulators of gene expression and tumorigenesis, and therefore a rich source of potential cancer drivers. DeVaux will use a mouse model to establish that the identified lncRNA plays a critical role in transforming pre-cancerous disease (that would not require surgery or radiation therapy) to aggressive breast cancer, which would require treatment.
“Successful completion of this project will lead to the provision of treatment to only the subset of patients whose DCIS is likely to progress to invasive breast cancer,” said DeVaux. “It will be possible to create an accompanying diagnostic test to help patients and their doctors decide if they need to undergo surgery, radiation therapy, or simply monitor their disease progression. This could be realistically achieved in the next ten years.”
Understanding the mechanisms by which lncRNAs facilitate tumor cells to become invasive and metastatic will also help identify new potential drug targets, or therapeutic entry points, to help treat those patients whose cancer has already progressed. Thus, the proposed study will impact breast cancer patients both short-term, by improving early stage patients’ quality of life, and long-term, by decreasing breast cancer patient mortality.
