Identifying ways to enhance the effectiveness of radiation in women with aggressive forms of breast cancer.  

Impact

Despite treatment that includes radiation therapy, many women with aggressive forms of breast cancer will experience a recurrence in the breast. Dr. Pierce has been focused on the causes of radio-resistance in breast cancer and developing radio-sensitization strategies for treating patients.  With BCRF support, she has focused on the use of anti-estrogens and anti-androgens in combination with radiation to treat breast cancer. The androgen receptor (AR), a known driver of prostate cancer, is also present in many breast cancers. Dr. Pierce has found that both types of drugs can indeed make radiation more effective but by different mechanisms and dependent on the breast cancer subtype. Therefore, Dr. Pierce and her colleagues investigated whether targeting AR and ER (estrogen receptor) may be an effective radio-sensitizing strategy for treating aggressive forms of ER-positive and AR-positive breast cancer. Dr. Pierce and her colleagues are conducting similar studies to increase the effectiveness of radiation therapy for treating other aggressive forms of breast cancer, such as triple-negative breast cancer (TNBC).    

Progress Thus Far

Dr. Pierce and her colleagues have shown that the AR-inhibitor, enzalutamide (Xtandi®) improved sensitivity to radiation in AR-positive breast cancers that lack estrogen receptor (ER-negative). A similar effect was not seen in AR-positive/ER-positive breast cancers, suggesting this approach may benefit TNBC patients.  

What's next

Her team will continue to investigate the mechanisms by which ER and AR promote resistance to radiation therapy and ways to identify patients likely to respond to ER and AR blockade plus radiation. In the next year, they will expand their studies in TNBC and test targeted therapies in combination with immune checkpoint blockade as a novel strategy to sensitize TNBC cells to radiation.