Ross Berkowitz, MD

2009-2010 BCRF Project:
Co-investigators: Ursula Matulonis, MD, and Zhigang Charles Wang, MD, PhD, Dana-Farber Cancer Institute and Brigham & Women's Hospital/Harvard Medical School, Boston, MA

The group at the Dana-Farber Cancer Institute and Brigham and Women's Hospital is examining the genetic link between breast and ovarian cancer which has been for a long time recognized by patients and their doctors. Ovarian cancer is a lethal disease with a mortality rate that exceeds all other gynecologic cancers but when treated at initial diagnosis, is highly sensitive to platinum-based chemotherapy much like a type of breast cancer called basal-like or triple-negative breast cancer that is diagnosed in women who have BRCA1 or BRCA2 mutations.

With support from The Breast Cancer Research Foundation, the researchers have generated a dataset of ovarian cancers, and found the two diseases, so-called "basal-like" breast cancer and high-grade serous ovarian cancer, are similar in a number of respects with genetic similarities, particular these two types of cancers do in fact show that they have similar unstable chromosomes. They have found a certain genetic abnormality on chromosomes 4, and 19 shared by both diseases and are in the process of investigating this further.

Recently, evaluation of total number of chromosomal breakpoints was found to be a good genomic marker for chromosomal instability to predict treatment response to the chemotherapeutic drug cisplatin in basal-like breast cancers. The researchers propose to explore whether this measure may also be useful for prediction of disease recurrence in ovarian cancer patients received cisplatin treatment. They will continue to collect more ovarian cancer samples in order to study a larger set of cancers for outcome when comparing them to triple negative breast cancer.

Mid-Year Progress Report:
At initial diagnosis, ovarian cancer is very highly sensitive to chemotherapy that consists of a platinum and a taxane, especially the most common type of ovarian cancer called high grade serous cancers which are also typically diagnosed in women with BRCA mutations. Unfortunately, most patients with advanced ovarian cancer develop a recurrence of their cancer because of the persistence of chemotherapy-resistant cells that eventually regrow. Triple negative breast cancer has been also found to be highly sensitive to platinum. Thus, given the clinical similarities between high grade serous ovarian cancer and triple negative breast cancer, the researchers postulated that genetic similarities must exist as well.

They have found the two diseases, so-called "basal-like" breast cancer and high-grade serous ovarian cancer, are similar in a number of genetic similarity and have similar unstable chromosomes. Recently, evaluation of total number of chromosomal damage measured as allelic imbalance (AI) was found to be a good genomic marker for chromosomal instability to predict treatment response to cisplatin in basal-like breast cancers. The scientists are exploring whether this measure may also be useful for prediction of disease recurrence in ovarian cancer patients.

Bio:
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.