Characterization of the Tumor Microenvironment of De Novo Oligometastatic Breast Cancer in a Nationwide Cohort

PURPOSEOligometastatic breast cancer (OMBC) has a more favorable outcome than widespread metastatic breast cancer. Some patients with OMBC achieve long-term remission if treated with multimodality therapy, including systemic and locally ablative therapies. However, not all patients with OMBC benefit from such treatment, while all experience toxicity. To explore biomarkers identifying patients with OMBC and potential long-term survival, we compared tumor-immune characteristics of patients with OMBC and long-term versus shorter-term survival.MATERIALS AND METHODSWe collected tumor tissue of 97 patients with de novo OMBC (<= 5 metastases) via the Dutch nationwide cancer and pathology registries using a case-control design. Long-term survivors (LTS) were defined as patients alive >= 10 years since OMBC diagnosis. Fifty-five LTS and 42 shorter-term survivors (STS) were included. Median follow-up was 15 years (IQR, 14-16). Tumor characteristics and infiltrating immune cells were assessed by immunohistochemistry and next-generation RNA-sequencing. Association of the resulting 52 biomarkers with long-term survival was assessed using logistic regression. Associations with survival within LTS were assessed using Cox-proportional hazards modeling. P values were adjusted for multiple hypothesis testing.RESULTSMost patients had estrogen receptor (ER)-positive OMBC (n = 86; 89%) and 23 (24%) had human epidermal growth factor receptor 2-positive disease. ER positivity in primary tumors distinguished LTS from STS. In addition, extracellular matrix (ECM)2-low and ECM4-high distinguished between long-term and shorter-term survival. Immune levels in the primary tumor did not associate with LTS. However, within the LTS subset, higher immune levels associated with improved progression-free survival.CONCLUSIONWe identified tumor and ECM features in the primary tumor of patients with de novo OMBC that were associated with long-term survival. Our data should be validated in other patients with OMBC before they can be used in clinical practice.