SPORE grant to fund breast cancer research

The National Cancer Institute has awarded a Specialized Programs of Research Excellence grant to the University Cancer Research Center for a series of projects designed to benefit women at high risk for breast cancer. The grant will provide $11.5 million over five years to support innovative, translational research with a global strategy.

The researchers will focus on women with genetic differences that increase their odds of developing aggressive breast cancer at a young age. They will search for better ways to prevent, detect and treat women at increased risk.

Principal investigator Olufunmilayo Olopade, the Walter L. Palmer Distinguished Service Professor in Hematology/Oncology and Human Genetics, will work closely with co-principal investigators Gini Fleming, Professor in Oncology/Hematology and Director of the Medical Oncology Breast Program, and Maryellen Giger, Professor in Radiology, to lead a team of 11 basic-clinical and population-science investigators at the University. This integrated effort focuses on developing genetic- and imaging-based approaches to the prevention, detection and treatment of breast cancers in genetically high-risk women.

The grant will support four research projects that focus on:

Using computerized image analysis of diagnostic mammography and magnetic resonance imaging to assess breast cancer risk,

• Finding better ways to detect cancer using ultrasound and magnetic resonance imaging,

• Understanding how genetic variations in hormones and hormone metabolism combine with environmental factors to influence the risk of breast cancer, and

• Identifying genetic variations that predict how patients will respond to chemotherapy.

Each of the four projects is directed by a team of scientists and clinicians, and is designed to combine basic laboratory and applied clinical studies. Each component builds on established strengths at the University in cancer, medical physics, advanced imaging, population genetics, pharmacogenetics and clinical trials.

“There will be more than 1.1 million new cases of breast cancer diagnosed worldwide this year,” Olopade said. “Although we have made enormous progress in understanding the genetic and molecular basis of this disease, we need to know so much more.

“This grant enables us to bring together investigators from many different fields to focus on finding new ways to help the people who need it the most, women at high risk for aggressive breast cancer.”

Project 1, led by Giger, Gillian Newstead, Professor in Radiology, and Charlene Sennet, Assistant Professor in Radiology and Mammography, will focus on developing multi-modality, image-based markers for assessing breast density and structure that may be used alone or together with clinical information, as well as biomarkers, to determine risk of breast cancer. The general hypothesis is that inclusion of automated analyses of the parenchyma will improve the assessment of breast cancer risk.

Project 2, led by Newstead, Gregory Karczmar, Professor in Radiology, and Nora Jaskowiak, Assistant Professor in Surgery, will look for ways to use magnetic resonance imaging to find very small early cancers or precancerous lesions. Findings from MRI scans also will be correlated with genetic and biologic markers found in tissue from biopsies.

Project 3, led by Olopade and Anna DiRienzo, Assistant Professor in Human Genetics and the College, will determine how variation in genes involved in the metabolism of hormones such as estrogen, and “xenobiotics”—influences from the environment, including drugs—affect the risk of breast cancer. This project will include study of the subjects’ genes, families and environmental exposure histories for a large cohort of African-American and Nigerian breast cancer cases.

Project 4, led by cancer pharmacologist Eileen Dolan, Professor in Hematology/Oncology and Mark Ratain, Professor in Hematology/Oncology, will identify genetic variants that influence how women and their breast tumors respond to cancer chemotherapy. Some women have genes that increase the side effects of cancer therapy; others have tumors that are not susceptible to treatment with certain drugs. This project will focus on studies, including clinical trials of new anti-breast-cancer drugs to see how differences in genes alter patients response to treatment.

In addition to these research projects, the SPORE grant includes a career-development program to recruit and train the next generation of breast cancer researchers.

The National Cancer Institute established the SPORE program in 1992 to promote interdisciplinary research and speed the transition of basic research findings from the laboratory to the clinic. The goal of the program is to bring new ideas that could reduce cancer incidence and mortality into clinical care, improving survival and enhancing quality of life.

“Funmi Olopade is the perfect person to lead this vast endeavor,” said Michelle Le Beau, Professor in Medicine and Director of the University Cancer Research Center. “She has an established reputation in breast cancer and genetic research, runs a highly productive basic science laboratory as well as an active clinical practice specializing in cancer risk and prevention.”

Olopade also is one of four co-directors of the Center for Interdisciplinary Health Disparities Research, a $9.7 million federally funded interdisciplinary effort to study why African-American women have an unusually high rate of breast cancer at an early age.

In 2005, she was awarded a MacArthur Fellowship for “translating findings on the molecular genetics of breast cancer in African and African-American women into innovative clinical practices in the United States and beyond.”