Ursula A. Matulonis, MD

2012-2013 BCRF Project:
(made possible by generous support from Play for P.I.N.K.)
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 goal of this research team at the Dana-Farber Cancer Institute and Brigham and Women's Hospital is to discover genomic predictors for response to therapy and potential therapeutic target(s) shared by high-grade serous ovarian tumors and triple-negative breast cancer. In the past year, Drs. Berkowitz, Matulonis, and Wang investigated mutations in a dataset using a genome-wide assay in a group of ovarian cancer patients treated in Boston, and they extended their analyses to a publically available genome sequencing dataset. The results suggest that the number of genome-wide gene mutations may reflect the degree of genomic instability and may also be useful to predict sensitivity to platinum-based chemotherapy in high-grade serous ovarian cancer. This genomic feature may also be applicable to triple negative breast cancer since these cancers possess DNA repair deficiencies that are observed in high-grade serous ovarian cancer. Drs. Berkowitz, Matulonis, and Wang generated a genomic dataset of the new genome-wide assay from ovarian cancer tissues from ongoing clinical trials with PARP inhibitors, which are drugs that stop repair of DNA in tumor. They have also included genome sequencing for mutation analysis in these studies.

Mid-year Progress: This team continues to work on the discovery of predictors for response to therapy and potential therapeutic targets shared by high-grade serous ovarian tumors and triple negative breast cancer. Recently, a mutation analysis was done using a publically available set of data from the National Cancer Institute. This dataset contains a large amount of genetic information, which was scrutinized with the hypothesis that the number of genetic mutations predicts response to treatment and the outcome of patients with breast and ovarian cancer. This group found that total mutation number in tumor genomes reflects the amount of genomic instability in both ovarian and breast cancers. As the mutation burden increases, so does the sensitivity to ovarian cancer chemotherapy, and patient survival increases as well. Surprisingly, this measure seems to predict chemotherapy response and survival in the subset of ovarian cancer patients with deficiency in one of the two key DNA repair genes called BRCA1 and BRCA2. These two genes are also the inherited causes of breast and ovarian cancer. Drs. Berkowitz, Matulonis, and Wang are analyzing data from breast cancer patients to see if the same relationship between good outcome and higher mutation burden is maintained. The working hypothesis is mutation burden reflects fidelity of DNA repair, which in turn predicts the outcome of certain chemotherapies and new agents like PARP inhibitors in both breast and ovarian cancer. The breast and ovarian group in Boston published an influential manuscript describing some of their work in ovarian cancer, acknowledging BCRF support, and already is talking to industrial partners about using their findings in upcoming clinical trials.

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.