Potential Morbidity Reduction With Proton Radiation Therapy for Breast Cancer

Abstract

Proton radiotherapy confers significant dosimetric advantages in the treatment of malignancies that arise adjacent to critical radiosensitive structures. To date, these advantages have been most prominent in the treatment of pediatric and central nervous system malignancies, although emerging data support the use of protons among other anatomical sites in which radiotherapy plays an important role. With advances in the overall treatment paradigm for breast cancer, most patients with localized disease now exhibit long-term disease control and, consequently, may manifest the late toxicities of aggressive treatment. As a result, there is increasing emphasis on the mitigation of iatrogenic morbidity, with particular attention to heart and lung exposure in those receiving adjuvant radiotherapy. Indeed, recent landmark analyses have demonstrated an increase in significant cardiac events that is linked directly to low-dose radiation to the heart. Coupled with practice-changing trials that have expanded the indications for comprehensive regional nodal irradiation, there exists significant interest in employing novel technologies to mitigate cardiac dose while improving target volume coverage. Proton radiotherapy enjoys distinct physical advantages over photon-based approaches and, in appropriately selected patients, markedly improves both target coverage and normal tissue sparing. Here, we review the dosimetric evidence that underlies the putative benefits of proton radiotherapy, and further synthesize early clinical evidence that supports the efficacy and feasibility of proton radiation in breast cancer. Landmark, prospective randomized trials are underway and will ultimately define the role for protons in the treatment of this disease.