(1089) Maternal cytokine expression in mice with gestational breast cancer

Objective: Immunosuppressive cytokines are implicated in both cancer progression and prenatal health outcomes. This study aims to examine cytokine levels in the plasma of tumor-bearing pregnant mice using a murine model of gestational breast cancer.

Study Design: On estrous day 11, nulliparous female BALB/c mice were either injected with 20K 4T1 MCherry tumor cells in PBS (20uL) a model for triple-negative breast cancer, or PBS (20uL) injected into the right 4th mammary duct (5 per group). These nulliparous BALB/c female mice were bred with BALB/c males (N=10). Mice were euthanized on gestational day 19: pup numbers and fetal weights were recorded and maternal blood was collected. Isolated serum was frozen and analyzed using a cytokine array (Proteome Profiler Mouse Array Kit).

Results: Three of 5 mice injected with tumor cells and 1 of 5 mice injected with PBS were pregnant at time of specimen collection. Mice injected with tumor cells developed small but grossly visible mammary tumors. The mouse injected with PBS had 5 pups weighing ~1.3g/pup, whereas mice injected with tumor cells had 1-6 pups weighing ~1.2g/pup. Cytokine array demonstrated absence of pro-inflammatory cytokines in both serum samples and similar expression of CXCL13 and GM-CSF. However, tumor-injected serum demonstrated decreased IL-10, an anti-inflammatory cytokine implicated in tumorigenesis and pregnancy outcomes (4.27 units control to tumor-injected serum expression), IL-3, and IL-4 (3.95 and 2.09 units control to tumor-injected, respectively), regulators of adaptive immunity.

Conclusion: There does not appear to be a difference in pro-inflammatory cytokine expression in serum of pregnant tumor-affected mice; however, there is decreased anti-inflammatory cytokine expression among individual markers. This was a pilot analysis on a small sample size; we plan to perform cytokine analysis on a larger murine sample size, to validate findings in the pregnant human population, and to examine murine cytokine expression of amniotic fluid and pups in this gestational breast cancer model.