Olufunmilayo (Funmi) I. Olopade, MD, FACP

Breast cancer can be regarded as a genetic disease caused by the accumulation of multiple genetic alterations. However, genes do not work in isolation, but rather their expression is often altered by influences from the environment.

Dr. Olopade’s studies address some of the most difficult remaining questions in breast cancer. Why do young women get breast cancer and what are the similarities between breast cancer in young women with BRCA mutations and breast cancer among young women in the general population without a family history? How should we screen for these highly proliferative tumors that may not be detectable by routine mammography? Why are they more aggressive than other breast tumors and do they have differential sensitivities to standard chemotherapy such that we should focus on drugs that target DNA repair pathways? Why are women of African ancestry more likely to develop the ER negative, HER2 negative basal-like breast cancers? In general, breast cancer in young women, especially those of African descent remains under-researched when one takes into account its impact on years of life lost and morbidity, its impact on young families, and its likely genetic causes with implications for relatives and future generations.

Towards this end, Dr. Olopade is conducting a BCRF-funded study targeting the Fanconi Anemia-BRCA1 pathway in breast cancer. This program represents an integrated attempt to translate recent advances in studying gene and environment interactions to the benefit of women, particularly young women, who are at risk of aggressive early onset breast cancer. Because only 5-10% of breast cancers are caused by inherited mutations in BRCA1 and BRCA2, the researchers are also pursuing mechanistic studies to identify alternative pathways for inactivation of BRCA1 to follow up on their observation that promoter methylation is associated with reduced BRCA1 gene copy number, reduced transcripts and chromosome 17 aneusomy, as shown in tumors from BRCA1 mutation carriers. It is expected that the accurate definition of genetic risks for young women will eventually lead to better clinical risk assessment and the development of more effective strategies for prevention, early detection and treatment of breast cancer for all women.

In a second project funded by BCRF, this year Dr. Olopade's team has successfully established a research infrastructure in Nigeria. Breast cancer is a major global health problem and a leading cause of death among women of all ethnic and racial backgrounds. With an estimated 1,152,161 new cases diagnosed worldwide per year, there is an urgent need to develop a global strategy to reduce the burden of breast cancer.

As a unique practice model, Dr. Olopade and her colleagues have established the first collaborative team of investigators qualified to conduct breast cancer clinical trials in Nigeria, the most populous county in sub-Saharan African with a population of 140 million, and have completed recruitment and training of competent and highly motivated staff to run clinical trials in Nigeria. They have successfully established the first fully functional immunohistochemistry laboratory at the University College Hospital to assist in the management of breast cancer patients. They are creating a Centre of Excellence in Breast Imaging in Ibadan, where mammographic imaging in conjunction with ultrasonography has begun in earnest. Lastly, they have final approval for the first PHASE II study to evaluate response to capecitabine as neo-adjuvant therapy in women with newly diagnosed locally advanced breast cancer.

Mid-Year Progress Report:
Breast cancer is a genetically and clinically heterogeneous disease. Whether different target cells contribute to this heterogeneity in different populations, and which cell types are most susceptible to oncogenesis is still not well understood. The importance of epigenetic regulation in breast cancer progression is increasingly recognized. Unlike genetic alterations, epigenetic aberrations are potentially reversible, allowing the malignant cell population to revert to a more normal state. With the advent of numerous drugs that target specific enzymes involved in the epigenetic regulation of gene expression, the utilization of epigenetic targets is emerging as an effective and valuable approach to early detection, treatment or prevention of breast cancer. Dr. Olopade's BCRF-funded studies aim at establishing a platform for understanding transcriptional regulation of BRCA1, especially the mechanism of BRCA1 promoter methylation.

Through the support of BCRF, Dr. Olopade and her team also have established the first collaborative team of investigators qualified to conduct breast cancer clinical trials in West Africa. The first trial, a PHASE II study to evaluate the efficacy, safety, and genomic markers of response of capecitabine as neoadjuvant therapy in women with newly diagnosed locally advanced breast cance,r is well under way. Unfortunately only one in ten women screened for the study qualifies because the majority of women in Nigeria are diagnosed in the most advanced stage of breast cancer. Dr. Olopade’s goal in the coming years is to change the face of breast cancer in Nigeria by increasing awareness of this disease and improving the standard of care through conduct of scientifically rigorous clinical trials.

Bio:
Funmi Olopade directs a multidisciplinary clinical and laboratory research program in cancer genetics at the University of Chicago Medical Center. This program helps speed the transfer of basic research in cancer genetics to the benefit of people. Dr. Olopade combines extensive family studies with genetic testing to develop strategies for prevention and/or early detection in patients at high risk for cancer.

Dr. Olopade is an international leader in the field of clinical cancer genetics, a field that seeks to identify and understand the various genes that contribute to cancer susceptibility, how these genes interact with one another and how they are affected by environmental factors. Her current laboratory research is focused on tumor suppressor genes such as BRCA1 and BRCA2 that predispose to breast and ovarian cancers. As a hematologist/oncologist, Dr. Olopade specializes in the treatment of aggressive breast cancer that disproportionately affects young women.

Dr. Olopade received her medical degree with distinction from the University of Ibadan in Nigeria and served as a medical officer at the Nigerian Navy Hospital. She came to the United States as a resident in internal medicine at Cook County Hospital, Chicago, where she was named Chief Medical Resident. She did her Hematology/Oncology Fellowship training at the University of Chicago and was appointed to the faculty in 1991. A former James S. McDonnell Foundation Scholar, Dr. Olopade currently is a Doris Duke Distinguished Clinical Scientist.

Dr. Olopade is a member of many professional societies including the American Association for Cancer Research, American Society of Clinical Oncology, the American Society of Hematology, American College of Physicians and the American Society of Breast Diseases. She serves on the Steering Committee of the NCI Cooperative Family Registry for Breast Cancer Studies and the Advisory Committee of the Cancer Genetics Network. Dr. Olopade is a member of the NCI Board of Scientific Counselors.