Pregnancy is a well established protective factor against breast cancer. One explanation for protection is the increased differentiation status of the parous epithelium. However, this does not explain the association of parity with increased aggressiveness of breast cancers, particularly cancers that occur soon after pregnancy. Because tumor aggressiveness can be influenced by the cell population that surrounds the mammary epithelium, we examined the potential role of the immune system in establishing a long-term difference between the mammary glands of primiparous and virgin animals. Specific mRNA levels, enzyme activities and antigen expressing cells were quantified in primiparous and virgin mammary glands from Sprague-Dawley rats in diestrous. Our results show that macrophages, but not neutrophils or B-cells, are specifically increased in fully involuted glands compared with age-matched virgin mammary glands. Macrophages play a dual role in tumor progression, both opposing and supporting the process. Our finding of an increased macrophage population in the primiparous mammary gland could explain the dichotomy of the reported association of parity with decreased breast cancer incidence and increased breast cancer aggressiveness.

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