Abstract Introduction Per NCCN guidelines, patients with stage I-III breast cancer should only have staging work up with CT chest, abdomen, and pelvis and bone scan if there are concerning symptoms, lab abnormalities, or physical exam findings. These patients do not require staging imaging because previous studies have documented the low incidence of metastatic disease found on systemic imaging, and the use of routine staging imaging has been shown to have a high false positive rate resulting in additional imaging and further work up with a low true positive rate. Despite the NCCN guidelines, extensive imaging is often performed prior to embarking on neoadjuvant therapy to look for evidence of metastatic spread of disease prior to surgery regardless of clinical stage and lack of symptoms. Methods We performed a retrospective analysis of patients at the University of Virginia diagnosed with invasive breast cancer who were recommended for neoadjuvant therapy and underwent systemic imaging to assess for the presence of distant metastatic breast cancer between 2012 and 2019. All receptor subtypes were included. Patients with signs/symptoms of metastatic disease at time of initial consultation were excluded. We evaluated the rate of metastatic breast cancer detected on systemic imaging. We also evaluated the rate of incidental findings on systemic imaging and how often this resulted in additional imaging or biopsy. Results 328 patients met inclusion criteria and were recommended for neoadjuvant chemotherapy and underwent systemic staging. Of these, 8 patients had bilateral breast cancer at time of diagnosis. Included patients were 54.2% hormone receptor (HR) positive, 35.4% triple negative, and 23.2% HER2 positive; 74.1% were node positive (Table 1). Metastatic breast cancer was identified in 9.1% (30 patients), which included 19 HR positive, 8 HER2 positive, and 7 triple negative patients. Of the patients found to have metastatic breast cancer, 80% had anatomic stage III disease at presentation and 93.3% were node positive. Two metastatic patients that were node negative had a cT2 or cT3 primary tumor. Systemic imaging identified incidental findings in 72.6% (238) patients. Most common incidental findings were pulmonary nodules (107), bone lesion or abnormality (71), hepatic lesions (55), and gynecologic lesions (50). Of the patients with incidental findings, 40.7% (98) underwent additional imaging for further work up or monitoring and 12.2% (29) underwent a biopsy or procedure for further work up. These biopsies identified benign or non-diagnostic results in 20 cases (69.0%) and identified an alternative malignancy in 9 cases (31%). Conclusions Within this study, asymptomatic metastatic disease was most commonly found in node positive stage III breast cancer, but was never or rarely found in stage I or II breast cancer patients. This validates NCCN recommendations that asymptomatic anatomic stage I or II breast cancer patients do not benefit from systemic staging. Yet, we did find a relatively high proportion of metastatic disease in asymptomatic patients with stage III breast cancer, indicating that systemic staging may be appropriate for this population. This must be balanced against the high probability of incidental findings with frequent additional imaging or biopsy, which has implications for patient anxiety, potential harm, and cost. Table 1: Patient Characteristics Citation Format: Courtney Lattimore, Squeo Gabriella, Christiana Brenin, Shayna Showalter, Trish Millard. Systemic staging in breast cancer patients receiving neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD16-05.