Loss of RB in Triple Negative Breast Cancer Associated with Favorable Clinical Outcome

Researchers at the Thomas Jefferson University Hospital and Kimmel Cancer Center at Jefferson have shown that loss of the retinoblastoma tumor suppressor gene (RB) in triple negative breast cancer patients is associated with better clinical outcomes. This is a new marker to identify the subset of these patients who may respond positively to chemotherapy.

Today, no such marker is applied in care of triple negative breast cancer, and as a result, patients are all treated the same.

Agnieszka Witkiewicz, M.D., Associate Professor of Pathology, Anatomy and Cell Biology at Thomas Jefferson University, and Erik Knudsen, Ph.D., Professor of Cancer Biology and Deputy Director of Basic Science at Jefferson’s Kimmel Cancer Center, presented the findings at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium during a poster discussion on Dec. 9.

“This is a step in trying to better direct treatment for patients with triple negative breast cancer,” Dr. Knudsen said.

In general for cancer, loss of tumor suppressor genes is associated with poor clinical outcome. However, loss of RB in triple negative breast cancer patients appears to be a predictor of favorable clinical outcomes.  This is because it changes the way tumor cells respond to therapy such that they end up becoming more sensitive to chemotherapy.

The researchers retrospectively evaluated the RB status and clinical outcome of a cohort of 220 patients diagnosed and treated at Thomas Jefferson University Hospital with chemotherapy.  RB loss, they found, was associated with a longer overall survival. In contrast, patients with RB had worse survival.

“Triple negative breast cancer is the most deadly of breast cancers, with fast-growing tumors, that affects younger women,” said Dr. Witkiewicz. “This work allowed us to identify a marker that could lead to better treatment for patients. It’s about female personalized medicine.”

Edith Mitchell, M.D., Professor of Medical Oncology at Jefferson, and Adam Ertel, Ph.D., a research instructor in the Department of Cancer Biology, were also involved in the study.

The next step for the researchers is a clinical trial at Jefferson to confirm their findings. Tumors of newly-diagnosed patients with triple negative breast cancer will be tested for the RB gene before they receive chemotherapy. After treatment, the data will be evaluated to determine the efficacy of directing future patient care.

This study represents one important example of personalized medicine being performed at the Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University and the Kimmel Cancer Center to improve patient care.



Radiation Oncology Announcements and Appointments

New faculty:

Thomas Jefferson University welcomes two new, seasoned clinicians and researchers to its Department of Radiation Oncology: Nicole Simone, M.D., from the National Institutes of Health’s National Cancer Institute (NCI) and Bo Lu, M.D., Ph.D, from Vanderbilt University.

Nicole Simone, M.D.

Dr. Simone is a board-certified Radiation Oncologist who has treated mostly patients with breast and head and neck cancers, while her research involves radiation’s effect on microRNAs in breast cancer and caloric restriction and radiation therapy—and the ability of both to delay breast cancer tumor growth.

“Dr. Simone is rapidly being recognized as one of the rising stars in the field,” said Adam Dicker, M.D, Ph.D, Professor and Chairman of the Department of Radiation Oncology. “Her research cuts across a number of cutting edge fields, including breast and prostate cancer biology, metabolism, microRNAs and computational biology.  The connection between diet and cancer treatment is very relevant for patients.”

Bo Lu, M.D., Ph.D

Dr. Bo Lu is also a board-certified Radiation Oncologist who comes to Jefferson from Vanderbilt University in Nashville, Tenn., where he was an Ingram associate professor with tenure in the Department of Radiation Oncology and Cancer Biology of the University’s School of Medicine.  He was also an attending radiation oncologist at the Vanderbilt University Medical Center, member of the Ingram Cancer Center, and director of the Translational Research Program and Lung Cancer Research Program.

“I am delighted that Dr. Lu has joined our faculty,” said Dr. Dicker. “He is internationally renowned for his work in clinical and translational radiation oncology, and I have received numerous congratulatory calls and emails from Chairs of Departments of Radiation Oncology around the world recognizing his numerous achievements.”

Dr. Lu’s focus is on radiation-induced cell death in lung patients, among other basic science areas. His clinical interests include the integration of novel targeted agents in the treatment of lung cancer, radiosurgery for lung cancer, and reductionof toxicities from thoracic radiation. More recently, Dr. Lu has looked at cancer stem cells for enhancing radiotherapy in a setting of lung cancer.

Appointments:

Congratulations to Maria Werner-Wasik, M.D., professor in the department of radiation oncology, and radiation oncology residency program director, who was elected as the Radiation Therapy Oncology Group Vice-Chair for Publications. (www.rtog.org)

Maria Werner-Wasik, M.D.

Dr. Werner-Wasik is a member of the RTOG Lung Cancer Steering Committee.  She succeeds William Sause, M.D., of Intermountain Medical Center in Salt Lake City, Utah, who has served as the RTOG publications vice-chair since 1999.

Dr. Werner-Wasik will chair the RTOG Publications Committee which is responsible for the oversight ofpublication quality and timeliness of the results of the group’s trials.

Drs. Timothy Showalter and Robert Den have been selected as recipients of the American Brachytherapy Society sponsored High Dose Rate fellowship program (1 week) for 2011.