October 2, 2015 | by Kelly Lopez
In the global fight against breast cancer, City of Hope scientists and doctors are on the forefront, conducting research that will ultimately result in less invasive and more effective treatments for women worldwide.
Some of their most promising work includes research on halting the spread of breast cancer, identifying disparities in treatment and survival among specific groups of women, use of gene expression to prevent cancer, and reprogramming normal cells to fight the disease.
Breast Cancer Awareness Month offers an ideal opportunity to learn more about their research – and the improved options and better future it portends. For some women, the future is already here, with innovations such as immunotherapy and the ability to identify specific biomarkers that signal cancer risks.
Among City of Hope’s research into potential new therapies and prevention strategies:
Identifying risks and disparities in Latina women
Jeffrey Weitzel, M.D., director of the Division of Clinical Cancer Genetics, is investigating disparities in cancer incidence among Latina women, including the role of BRCA gene mutations, which increases the risk of breast and ovarian cancers.
Already, his research has produced an alarming statistic: In the group he studied, nearly one-third of the women with ovarian cancer had a BRCA mutation. Compared to the prevalence in non-Latinas, the percentage was higher than expected, and it’s an indication that genetic cancer risk assessment is needed in the Latina population, Weitzel said.
Weitzel recently published a paper about this in Cancer, the journal of the American Cancer Society.
Now, with support from the Avon Foundation and from the Breast Cancer Research Foundation, Weitzel is working with the National Cancer Institute of Mexico City, the University of Guadalajara and Tec Salud in Monterrey to help develop cancer risk counseling services for this population.
“Mexican women with a BRCA mutation would benefit from increased breast cancer screening and the removal of the tubes and ovaries after completion of childbearing, which is known to reduce the risk of both ovarian and breast cancers,” he said. “This single procedure could significantly save lives.”
Weitzel is also collaborating with Susan Neuhausen, Ph.D., The Morris & Horowitz Families Professor in Cancer Etiology & Outcomes Research, to identify additional genetic mutations that may lead to breast cancer in Latinas. These women are typically underrepresented in research studies.
In one study, Neuhausen and Weitzel identified what’s called a founder mutation — meaning it’s observed with high frequency in a particular population — for the PALB2 gene, a breast cancer susceptibility gene.
Neuhausen recently received a five-year, $4 million grant from the National Cancer Institute to expand this research. “We’re trying to discover additional breast cancer predisposition genes for risk assessment and precision medicine,” she said.
Developing innovative treatments
Joanne Mortimer, M.D., director of the Women’s Cancers Program, is working on a new way of identifying which breast cancer patients might respond better to specific treatments.
Using a novel PET imaging agent, 64Cu-DOTA trastuzumab, developed at City of Hope, Mortimer and her colleagues use PET scans to highlight areas of the body with HER2 positive cancer cells.
This approach improves therapy by identifying whether a woman should be treated with HER2-specific treatments — as well as where the cancer has spread, information that biopsies from a single site can’t provide.
New methods of fighting breast tumors
Molecular oncology researchers focus on cancer-associated activity in a cell’s nucleus. One especially prominent factor in many breast and ovarian cancers is the BRCA1 tumor suppressor, which prevents cells from properly repairing breaks in chromosomal DNA. That, in turn, encourages the accumulation of even more cancer-causing mutations.
But Jeremy Stark, Ph.D., associate professor of the Department of Cancer Genetics and Epigenetics, is finding that biologically speaking, two wrongs can make a right. In a study published recently in the Journal of Biological Chemistry, Stark found that inactivating factors in a signaling pathway called 53BP1/RNF168 could block lethal failure in DNA repair caused by mutations in the BRCA1 gene.
This discovery could lead to more effective drug regimens for women with BRCA1 mutations.
Searching for a family history of breast cancer
Many patients with breast cancer have a family history of the disease. This is known as hereditary breast cancer, which is mainly caused by mutations of BRCA 1 and 2 genes.
Looking into this history requires detective-like inquisitiveness and a passion for finding the causes of disease. Xiaochun Yu, M.D., Ph.D., a professor in the Department of Cancer Genetics and Epigenetics, has this unique skill set. He is a lead authority in cell mutations that may make chemotherapy more effective.
Yu has discovered that carriers of BRCA 1 and 2 mutations often develop breast cancer at a very young age, and that hereditary breast cancer is often resistant to conventional therapy. His research focuses on how these mutations initiate familial breast cancer, as well as potential therapeutic approaches to halt cancer development.
Research has recently shown that certain inhibitors selectively suppress BRCA1 tumors, and Yu has found different efficacy of inhibitors for tumor cells with different BRCA mutations.
Ultimately, this work may lead to selectively using specific inhibitors for patients with certain BRCA mutations.
Research Revolutionizes Treatment
These research projects are but some of the avenues of inquiry currently being pursued by City of Hope’s researchers and physicians.
“These advancements drive a new level of compassionate care for women,” Mortimer said. “City of Hope is creating less invasive, more effective therapies that are revolutionizing patient care.”