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It is well established that pregnancies protect against breast cancer; however, the mechanism involved is not completely understood. We investigated the influence of parity on hormonal and proliferation markers in benign tissue from tumor blocks of breast cancer cases. Women with breast cancer were recruited from a case-control study nested within the Multiethnic Cohort study. Tissue microarrays of benign tissue cores were available for 159 participants. Immunostaining for estrogen receptor α (ERα) and ERβ, progesterone receptor, human epidermal growth factor receptor 2 (Her2/neu), Ki-67, and proliferating cell nuclear antigen (PCNA) in epithelial tissue was evaluated by a pathologic expert. We applied logistic regression models to examine marker expression by parity (0, 1-2, and ≥3 live births with adjustment for age at diagnosis and BMI). Of the 159 women, 24 were nulliparous, 63 had one or two live births, and 72 had three or more live births. Inverse associations were observed between parity and expression of ERα (Ptrend=0.02) and PCNA (Ptrend=0.04). Among nulliparous women, 45.5% were ERα positive in contrast to 18.0 and 18.9% of women with one or two and at least three live births, respectively. The respective values for PCNA were 56.5, 44.3, and 31.1%. No associations were detected for ERβ, progesterone receptor, Her2/neu, and Ki-67. The current findings suggest that pregnancies may protect against breast cancer by reducing susceptibility to estrogenic stimuli and proliferative activity as assessed by the expression of ERα and PCNA in breast tissue.

Parity and expression of epithelial histopathologic markers in breast tissue