"The Biology of Radiotherapy-Associated Side Effects in Breast Cancer Patients"

Mylin A. Torres, M.D.
Associate Professor
Department of Radiation Oncology
Director of the Glenn Family Breast Center
Winship's Glenn Family Breast Center
Emory University School of Medicine

Currently, there are 3 million survivors of breast cancer, and this growing population has recognized a need for strategies aimed at identifying patients at risk for radiation (RT) side effects and for preventing long term sequelae of treatment.  Acute RT dermatitis is one of the most common side effects of RT and may be a cause of poor compliance with treatment.  During RT, approximately 70% of patients develop significant cutaneous toxicity including moist skin desquamation, erythema, and hyperpigmentiation. Moreover, up to 40% of women will develop long term breast side effects including skin thickening, telangiectasias, fibrosis, induration, breast contracture, and pain.  Studies have shown that predictors of RT-induced skin toxicity include large breast size and prior chemotherapy treatment as well as factors related to RT treatment itself (e.g. radiation dose per fraction and total dose delivered).  Nevertheless, the underlying biological mechanisms that underlie RT-induced skin changes remain unclear, and clinicians are still unable to reliably identify patients who are at risk for significant RT-induced breast disfigurement, pain, and poor quality of life.  The recent development of the 21 gene recurrence score which assesses an individual breast cancer patient’s risk of distant recurrence has revolutionized the ability of clinicians to personalize treatment.  However, no such assay exists for predicting an individual patient’s risk of significant toxicities from cancer therapies.  Indeed, a patient’s unique biological response to RT may significantly impact the development of RT-induced breast toxicities and ultimately breast disfigurement and pain.  Using ultrasound tissue characterization, we have obtained objective measures of skin changes in two prospectively studied cohorts of breast cancer patients before, during, and after RT.  We have identified patient and treatment characteristics associated with short and long term RT skin toxicity.  We are currently evaluating biological predictors of RT-skin toxicity. This information will allow clinicians and patients to make important and tailored decisions regarding clinical management of breast cancer.  The data will also serve as foundation for the development of proactive preventative strategies early in cancer treatment to prevent breast disfigurement and pain.  Of direct clinical relevance, early stage breast cancer patients who are reliably identified as being at significant risk for RT-induced skin changes, may elect for mastectomy (as opposed to breast conserving surgery), which precludes the need for treatment with RT.