Ursula A. Matulonis, MD

2009-2010 BCRF Project
Co-investigators: Ross Berkowitz, 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:
Ursula Matulonis, MD, is an Associate Professor of Medicine at Harvard Medical School and the Medical Director and Program Leader of the Gynecologic Oncology Program at Dana-Farber Cancer Institute. Her research is focused on gynecologic malignancies, and she is the Principal Investigator of several clinical trials for ovarian and cervical cancer. These trials include novel drug development as well as tissue banking and quality of life studies within ovarian cancer. Dr. Matulonis also has a strong interest in ovarian cancer translational research projects, two of which involve the molecular profiling of ovarian serous cancers as well as identification of oncogenic, targetable mutations in ovarian cancers.

Dr. Matulonis is a recipient of the Dennis Thompson Compassionate Care Scholar award, and was named one of Boston's "Best Physicians" in Medical Oncology by Boston Magazine. She also received two Partners in Excellence Awards for her steadfast work at Dana-Farber.

Dr. Matulonis currently serves on the National Comprehensive Cancer Network Ovarian Cancer Recommendation and Guideline Committee, the Society of Gynecologic Oncology National Meeting Planning Committee, the American Society of Clinical Oncology Education Committee for Gynecologic Oncology, the Gynecologic Oncology Group Quality of Life Committee, and is the Medical Director and Advisor for the non-profit organization Ovations for the Cure.

After receiving her MD from Albany Medical College in New York she completed an internship and residency at the University of Pittsburgh, followed by a medical oncology fellowship at Dana-Farber. She has been an attending physician at both Dana-Farber and Brigham and Women's Hospital since 1994.