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Lori J. Pierce, MD, FASCO, FASTRO
Member, BCRF Scientific Advisory Board
Professor of Radiation Oncology
Vice Provost for Academic and Faculty Affairs
University of Michigan
Ann Arbor, Michigan
Member, BCRF Scientific Advisory Board
Goal: To identify ways to enhance the effectiveness of radiation in women with aggressive forms of breast cancer.
Impact: Dr. Pierce is conducting studies to identify clues from the tumor that could be used to predict breast cancer recurrence following radiation therapy. Her work may improve outcomes by identifying patients at high risk of recurrence who need more aggressive therapy, and it could also lead to new treatments for this group of patients.
What’s next: She and her team will investigate treatment approaches that can reverse resistance to radiation therapy. In addition, they will determine if specific tumor receptors can affect the response of patients to radiation therapy.
Radiation therapy after the surgery reduces the risk of local recurrence in the breast. While effective, some women do experience local recurrence. The androgen receptor may play a role in resistance to radiation therapy. Dr. Pierce is investigating the mechanism by which AR promotes resistance to radiation therapy and identifying patients likely to respond to AR blockade plus radiation.
Full Research Summary
Research area: Understanding the mechanisms of radiation resistance in women with aggressive forms of breast cancer and how drug targeting can overcome this resistance.
Impact: Despite treatment that includes radiation therapy (RT), many women with aggressive forms of breast cancer will experience a recurrence in the breast. Dr. Pierce’s team is developing strategies to sensitize resistant cancers to radiation treatment, focusing on the androgen receptor (AR), a known driver of prostate cancer that is also present on many breast cancers. Studies show that AR may also play a role in radiation resistance of breast cancer. Therefore, Dr. Pierce and her colleagues are investigating whether targeting AR may be an effective treatment option for women with aggressive forms of AR-positive breast cancer. They are also looking at ways to sensitize radiation-resistant estrogen receptor-driven breast cancer cells.
Current investigation: Dr. Pierce’s team is working to identify novel drug targets that can increase the effectiveness of radiation therapy for women with aggressive forms of breast cancer.
What she’s learned so far: Dr. Pierce has been focused on the causes of radio-resistance in breast cancer and developing radio-sensitization strategies for treating patients. Her group has demonstrated that PARP inhibition led to increased radio-sensitization across a range of tumor subtypes. This finding led to multi-institutional trials to test PARP-inhibitor with RT. In other studies, Dr. Pierce and her colleagues have studied the role of the AR in radio-sensitization and shown that inhibition of AR makes some breast cancers more sensitive to radiation. Moreover, radio-sensitization utilizing an AR-inhibitor such as enzalutamide (Xtandi®) is effective in cancers that express AR and lack estrogen receptor (ER). Those cancers that express both the AR and the ER are not similarly sensitized by AR-inhibition.
What’s next: Her team will investigate the mechanism by which AR promotes resistance to radiation therapy and the role the ER plays in this process. They will extend their studies to AR-positive and ER-positive breast cancer using a novel AR inhibitor, Seviteronel. In addition, they will determine the effect of ER inhibition on resistance to radiation therapy using several ER-inhibitors. The results of these studies will inform future clinical trials of ER inhibitors with radiation as a novel strategy for treating patients with high-risk ER-positive breast cancer.
Dr. Pierce completed residency in Radiation Oncology at the University of Pennsylvania and was a senior investigator at the National Cancer Institute (NCI). She joined the Department of Radiation Oncology at Michigan in 1992, where she is currently Professor of Radiation Oncology and Vice Provost for Academic and Faculty Affairs.
She has published more than 170 papers and book chapters on aspects of radiotherapy (RT) in the treatment of breast cancer, and her work has been funded by the NCI, Department of Defense Funds for Breast Cancer Research, the Breast Cancer Research Foundation, Komen for the Cure, BCBS of Michigan and private industry.
Her research focuses on the use of RT in the treatment of breast cancer, with emphasis upon contemporary RT treatment planning techniques, the use of RT in the presence of a breast cancer susceptibility gene, and pre-clinical and clinical use of radiosensitizing agents.