De Novo Oligometastatic Breast Cancer

Metastatic breast cancer may present clinically either as recurrence after a previous diagnosis of stage I-III disease or as de novo metastatic breast cancer that is also called stage IV disease according to the American Joint Committee on Cancer (AJCC) tumor, node, metastasis classification. Recurrent metastatic disease arises from clinically undetectable distant micrometastases that were already present at the time of diagnosis, were not eradicated by systemic adjuvant therapies, and grew into clinically detectable  acrometastasis after a variable duration of tumor dormancy. In this conceptual framework, de novo metastatic breast cancer is a disease where micrometastases have no dormant period or the dormancy has passed before diagnosis. What determines the duration of cancer cell dormancy and how cells emerge from dormancy remain largely unknown. Approximately 6%-7% of newly diagnosed breast cancers present as de novo metastatic disease in the United States, and this proportion is larger in middle-income countries. While this fraction remained stable in the past 20 years, the absolute number of patients diagnosed with de novo metastatic breast cancer is increasing because of a growing population and more sensitive imaging technologies for staging, an estimated 18,000 patients will be diagnosed with stage IV breast cancer in 2023 in the United States. As adjuvant systemic therapies become more  effective in eradicating micrometastatic disease, metastatic recurrences in stage I-III breast cancers are decreasing, and the proportion of de novo metastatic cancers is increasing. Historically, about 20%of patients with newly diagnosed metastatic breast cancers had de novo disease; in comparison, the contemporary rates are closer to 30%-40%. Clinically, a fundamental difference between recurrent and de novo metastatic disease is exposure to prior therapies. Most patients with recurrent metastatic disease have been exposed to prior systemic therapy, and their recurrent disease represents growth of partially treatment resistant cells. Despite a potentially major difference in sensitivity to systemic therapies, current treatment guidelines for metastatic breast cancer do not distinguish between recurrent and de novo metastatic cancers. A further clinical subsetwithin de novo metastatic cancers is oligometastatic disease that could be rendered no evidence of disease (NED) with locoregional and metastases-directed therapy.