Abstract
Young African American women have an increased risk of developing and dying from “triple negative/basal breast cancer” compared to young Caucasian women, but the reason for this is unknown. Insight into this problem may be elucidated by the fact that breast cancers associated with a recent pregnancy are more likely to be metastatic. For all women, having had a recent pregnancy is an independent risk factor for poor prognosis. Epidemiologic data shows increased risk of triple negative/basal breast cancer with increased childbearing in African American women (Millikan et al 2008). We speculate that the hormones of pregnancy combined with the tissue-remodeling of the post-partum breast back to its pre-pregnant state (a normal process called postpartum involution that occurs after childbirth in the absence of breastfeeding, or at weaning in women who breastfeed) provides a two-hit tumor promotional tissue environment that results in increased metastasis of these tumors. Using an innovative, intraductal preclinical model developed in our laboratory, we tested whether a triple negative/basal breast cancer cell line (MCF10ADCIS.com) is promoted by pregnancy or postpartum involution. When these cells are injected into mammary ducts of nulliparous female mice, there is evidence of tumor progression from hyperplastic alveolar nodules to ductal carcinoma in situ to local invasion that is accompanied by progressive loss of the protective myoepithelial cell layer. Further, tumor burden in pregnancy and postpartum involution is much greater than their respective nulliparous controls. Importantly, with pregnancy and postpartum involution the protective myoepithelial cell layer surrounding tumors is compromised at earlier stages than in nulliparous controls. Physiologic changes to adherens junctions and myoepithelial cells occur during normal pregnancy and post-partum involution, respectively. These data suggest that the physiological environments of pregnant and involuting glands promote tumor progression and begin to unfold the biological mechanisms for the effects of parity on aggressive breast cancers.
Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B54.
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