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Received Oct 25, 2017; Accepted Apr 12, 2018
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1. Introduction
Radiation therapy is traditionally utilized in stages I–III breast cancer as a local therapy after surgical management to improve disease-free survival and in some cases overall survival. In the metastatic setting, it is used for effective palliation of symptomatic metastases. Advances in tumor biology and immunology have led some to suggest a role for radiotherapy in the metastatic setting to augment traditional systemic therapies such as chemotherapy or immune-modulating agents. While decades of research have demonstrated that a major component of local tumor control is mediated by irreparable damage to the DNA of malignant cells resulting in cell death [1], recent research has elucidated multiple radiation-induced effects on both tumor cells and the tumor microenvironment. Following ablative doses of radiotherapy, release of tumor antigens, tumor DNA, cytokines, and chemokines promote innate intratumoral immunity, leading in some cases to an adaptive response [2, 3]. This suggests that the immune response may play a part in high local control rates seen with radiation therapy. Immune-modulating therapeutics, such as checkpoint inhibitors, might therefore be incorporated with radiation to enhance the antitumor immune response with the intent of improving outcomes in patients with oligometastatic or polymetastatic disease [2]. Here we will review the rationale for the use of stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic breast cancer and explore the data to suggest that incorporating immunotherapy may expand the use of SBRT to polymetastatic disease.
2. Oligometastases in Breast Cancer
Breast cancer has provided one of the earliest models in our understanding of cancer progression and metastasis. Pioneering work by Halsted resulted in the theory of orderly spread of cancer from the initial primary tumor location to the regional draining lymph nodes, followed by metastatic spread to distant organs [4]. When subsequent radical surgical interventions and en bloc resections did not eliminate the occurrence of distant metastases, competing hypotheses by Keynes and subsequently Fisher proposed that breast cancer was likely already systemically disseminated at the time of diagnosis at the primary tumor [5, 6]. With this came...