William H. Baker Professor of Gynecology
Chief of Gynecologic Surgery, Brigham and Women's Hospital
Harvard Medical School
Co-Investigators: Ursula Matulonis, MD, and Zhigang Charles Wang, MD, PhD, Dana-Farber Cancer Institute, and Brigham and Women's Hospital/Harvard Medical School, Boston, MA
With BCRF support, physicians and scientists have joined forces at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital to study the common genetic features of breast and ovarian cancers. This team believes that they can accelerate progress by studying these cancers together and hope to leverage discovery in one disease to benefit the other. The Dana-Farber/Brigham and Women’s team is using all available information from collaborative clinical trials, publicly available data from consortia of investigators around the world, and unique technologies that they themselves and their collaborators are developing.
Drs. Berkowitz, Matulonis, and Wang published two research reports showing the burden of genetic mutations that accumulate in breast and ovarian cancers can influence the outcome of treatment. Specifically, they found that cancers with higher mutation burdens respond better to certain treatments, knowledge that has the potential to lead to treatment advances that will help patients live longer without cancer. This work has already been cited in high-profile reviews and scholarly articles. In ovarian cancer and certain breast cancers, two drugs are particularly useful and interesting. The first one is cisplatin, a platinum-based chemotherapy, and includes several derivatives that are used in both breast and ovarian cancer. The second group of drugs is comprised of newer agents called PARP inhibitors, which target the ability of cells to repair damaged genes and DNA. This team believes that the ability of breast and ovarian cancers to quickly repair their damaged DNA confers resistance to these agents; cancers that cannot repair as well build up damage and are more likely to be killed. They will test this hypothesis in a clinical trial that will study ovarian cancer tissue from patients receiving both drugs.
This team found that the amount of chromosomal damage in both triple-negative breast cancer and high-grade serous ovarian cancer predicted what the cancer response to cisplatin chemotherapy would be. The more unstable the DNA of the tumor is, the more sensitive to chemotherapy. “PARP” is an enzyme involved in aspects of DNA repair, and PARP inhibitors are now in clinical studies for the treatment of advanced ovarian cancer, specifically the high grade serous type. The researchers analyzed chromosomal patterns in an early-phase (Phase I) study of PARP inhibitors for women with advanced ovarian cancer. Investigators in Boston and other sites are completing a Phase II trial of PARP inhibitors (combined with another targeted drug), and this team proposes to complete genetic analysis of these cancers and relate their findings to the responsiveness of these cancers to PARP inhibitor treatment. They also located a very interesting genetic region which becomes altered in certain ovarian cancers and may cause or contribute to the cisplatin resistance that usually develops in ovarian cancer. They are excited to explore this genetic alteration further and to complete their study of the women participating in the PARP inhibitor trial.
Ross Berkowitz, MD is the William H. Baker Professor of Gynecology at Harvard Medical School and the Director of Gynecology and Gynecologic Oncology at Dana-Farber Cancer Institute and Brigham and Women's Hospital. In addition, he is also the Co-Director of the Women's Cancers Program at Dana-Farber and the Director of the Gynecologic Cancer Program at Dana-Farber/Partners Cancercare and Dana-Farber/Harvard Cancer Center.
During the past twenty years, the focus of his research has been in the areas of gestational trophoblastic disease and ovarian neoplasia. Investigations in gestational trophoblastic disease have dealt with identifying risk factors for development of these tumors as well as advancing understanding of the natural history of these diseases including subsequent reproductive experience. His research in ovarian neoplasia has concerned both the development of innovative and novel therapies as well as molecular biologic studies to identify genetic changes in ovarian neoplasia and differences in the pathways of development of borderline ovarian tumors, invasive ovarian cancers, and peritoneal cancers.
Dr. Berkowitz earned his MD from Boston University and had his residency training in surgery at the Peter Bent Brigham Hospital and then in obstetrics and gynecology at the Boston Hospital for Women. He completed his fellowship in gynecologic oncology at the Boston Hospital for Women and joined the faculty at Brigham and Women's Hospital thereafter.