November 28, 2017—(BRONX, NY)—Researchers at Albert Einstein College of Medicine, part of Montefiore, and Hackensack Meridian Health John Theurer Cancer Center at Hackensack University Medical Center have secured a five-year, $6.4 million grant from the National Institutes of Health (NIH) to identify biomarkers that can predict which women with pre-cancerous tissue in their breast will develop invasive breast cancer. This research could help personalize treatment and improve outcomes for tens of thousands of women each year.
Thomas Rohan, M.B.B.S., Ph.D., D.H.Sc.Ductal carcinoma in situ (DCIS)—increasingly detected thanks to the widespread use of mammography—is a precursor of invasive breast cancer (IBC). Approximately 50,000 women are diagnosed with the disease each year. When untreated, between 14 and 53 percent of patients develop IBC in the three decades following diagnosis. Unfortunately, it’s not possible to tell which DCIS patients will go on to develop IBC. As a result, individual women are often over- or under-treated—either suffering debilitating radiation or chemotherapy treatments they do not need, or skipping potentially life-saving therapies.
“A diagnosis of DCIS presents patients with a difficult and stressful dilemma in terms of how to treat the condition,” says co-principal investigator Thomas Rohan, M.B.B.S., Ph.D., D.H.Sc., professor and chair of epidemiology & population health and the Harold and Muriel Block Chair in Epidemiology and Population Health at Einstein. “A clinical test that could help accurately predict a patient’s prognosis would be enormously helpful and provide some much needed direction for settling on a plan of care.”
“A clinical test that could help accurately predict a patient’s prognosis would be enormously helpful and provide some much needed direction for settling on a plan of care.”– Thomas Rohan, M.B.B.S., Ph.D., D.H.Sc.
As part of their effort to develop a prognostic test for IBC risk, Einstein and Hackensack University Medical Center researchers will evaluate a promising experimental assay that measures the expression of three genes— p16, COX-2, and Ki67—implicated in cell proliferation. They will also instigate novel research into microRNAs, noncoding RNAs that regulate gene expression and are thought to contribute to the development of invasive cancer.
Such markers might also help improve treatment for women found to be at high risk for IBC—by leading, for example, to novel agents that target molecular changes associated with invasive-disease development.
“We have concentrated our efforts on developing state-of-the-art molecular tools to better understand the natural history of Ductal Carcinoma in situ (DCIS) lesions, with hope to complement current histological and immunohistochemical assays and improve personalized prognostic for women diagnosed with this disease” says co-principal investigator Olivier Loudig, Ph.D., formerly of the department of epidemiology & population health at Einstein, and now an associate scientist at John Theurer Cancer Center at Hackensack University Medical Center, and member of the Georgetown Lombardi Comprehensive Cancer Center.
Researchers will use clinical data and archived tissue samples from a cohort of more than 7,000 patients diagnosed with DCIS and who were followed to see if they later developed IBC. They will evaluate the samples to identify and validate miRNA expression changes associated with risk for subsequent IBC; evaluate risk of IBC in association with two previously identified sets of markers, including Oncotype DX DCIS score; and examine the association between clinical factors and risk for subsequent IBC.
The grant, titled “Molecular markers of risk of subsequent invasive breast cancer in women with ductal carcinoma in situ,” was awarded by the National Cancer Institute, part of the NIH (R01CA218429).