RT Journal Article SR Electronic T1 Treatment of Triple-Negative Breast Cancer Using Anti-EGFR–Directed Radioimmunotherapy Combined with Radiosensitizing Chemotherapy and PARP Inhibitor JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 913 OP 921 DO 10.2967/jnumed.112.111534 VO 54 IS 6 A1 Fares Al-Ejeh A1 Wei Shi A1 Mariska Miranda A1 Peter T. Simpson A1 Ana Cristina Vargas A1 Sarah Song A1 Adrian P. Wiegmans A1 Alex Swarbrick A1 Alana L. Welm A1 Michael P. Brown A1 Georgia Chenevix-Trench A1 Sunil R. Lakhani A1 Kum Kum Khanna YR 2013 UL http://jnm.snmjournals.org/content/54/6/913.abstract AB Triple-negative breast cancer (TNBC) is associated with poor survival. Chemotherapy is the only standard treatment for TNBC. The prevalence of BRCA1 inactivation in TNBC has rationalized clinical trials of poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors. Similarly, the overexpression of epidermal growth factor receptor (EGFR) rationalized anti-EGFR therapies in this disease. However, clinical trials using these 2 strategies have not reached their promise. In this study, we used EGFR as a target for radioimmunotherapy and hypothesized that EGFR-directed radioimmunotherapy can deliver a continuous lethal radiation dose to residual tumors that are radiosensitized by PARP inhibitors and chemotherapy. Methods: We analyzed EGFR messenger RNA in published gene expression array studies and investigated EGFR protein expression by immunohistochemistry in a cohort of breast cancer patients to confirm EGFR as a target in TNBC. Preclinically, using orthotopic and metastatic xenograft models of EGFR-positive TNBC, we investigated the effect of the novel combination of 177Lu-labeled anti-EGFR monoclonal antibody, chemotherapy, and PARP inhibitors on cell death and the survival of breast cancer stem cells. Results: In this first preclinical study of anti-EGFR radioimmunotherapy in breast cancer, we found that anti-EGFR radioimmunotherapy is safe and that TNBC orthotopic tumors and established metastases were eradicated in mice treated with anti-EGFR radioimmunotherapy combined with chemotherapy and PARP inhibitors. We showed that the superior response to this triple-agent combination therapy was associated with apoptosis and eradication of putative breast cancer stem cells. Conclusion: Our data support further preclinical investigations toward the development of combination therapies using systemic anti-EGFR radioimmunotherapy for the treatment of recurrent and metastatic TNBC.