Mammary tumor and mastectomy synergistically promote neuroinflammation in a breast cancer survivor model.

Understanding why breast cancer survivors are at an increased risk for cognitive and affective disorders is essential for developing targeted treatment plans and improving quality of life. Microglia priming results in chronic neuroinflammation and can contribute to neuronal degeneration and dysfunction, thereby offering a potential mechanism for altered brain function that persists after tumor removal. This study examined whether mammary tumors alter microglia and augment the inflammatory profile and behavior of mice. To test this, non-metastatic mammary tumor cells (67NR) were injected orthotopically into the mammary glands of BALB/c mice, allowed to grow for 16 days, and then the tumors were removed via mastectomy. Following a 14-day surgical recovery, the mice were challenged with lipopolysaccharide (LPS), and then central and peripheral inflammation, anxiety, and depressive-like behavior were evaluated. Here we show that major central and peripheral inflammatory markers were not altered by tumor growth nor mastectomy surgery alone. However, hippocampal mRNA expression of major proinflammatory cytokines IL-1β and TNFα was increased in tumor removal animals, persisting past surgical recovery. Nonetheless, the immune and behavioral responses following LPS administration were comparable among groups. In sum, these data demonstrate that the combination of tumor and mastectomy promotes neuroinflammation; however, immune challenge did not elucidate this inflammation as maladaptive for the host.