Abstract P1-05-01: Characterization of human postpartum breast involution: Implications for young women’s breast cancer

Abstract

Abstract Introduction: Women diagnosed with breast cancer within 5 years postpartum have poor outcomes. In rodents, postpartum mammary gland involution promotes tumor progression and metastasis, implicating breast involution in the poor prognosis of breast cancers diagnosed in postpartum women. Rodent mammary gland involution is characterized by wound healing programs that include epithelial cell death, immune cell infiltrate, and fibrillar collagen deposition; all attributes associated with breast cancer progression. Thus, the gland remodeling of postpartum involution may provide a plausible explanation for how postpartum breast involution promotes breast cancer. Here, we characterize human breast tissue across pregnancy, lactation, and the postpartum time-period to determine if remodeling of the secretory competent breast to a quiescent state involves loss of secretory lobules, and whether involution is mediated by wound healing-like programs. Methods: Adjacent normal breast tissues from pre-menopausal women (n = 140), aged 20-45 years, were grouped by reproductive categories of never-been-pregnant (NBP), pregnant, lactating, and by time since last delivery, and evaluated histologically and by special stain for epithelial area, lobular subtype composition, apoptosis, immune cell infiltration, and collagen deposition, using computer assisted quantitative methods. Statistical comparisons between multiple categories were done using one way ANOVA. Results: Dramatic increases in breast epithelial area and lobule differentiation were observed, with 5-8 fold increases for pregnancy and 10-13 fold for lactation, over nulliparous controls. By 12 months postpartum, epithelial content and lobular differentiation were indistinguishable from nulliparous controls, consistent with complete regression of the lobular structures developed in preparation for lactation. Analyses of apoptosis, immune cell infiltration, and collagen deposition confirmed human postpartum breast involution is characterized by wound healing-like, tissue remodeling programs. Conclusion: Human postpartum breast involution is a dominant tissue-remodeling process that returns the gland to a morphological state largely indistinguishable from the never-been-pregnant gland. Further, involution occurs within a defined window of time. Our data implicate postpartum breast involution as window of risk for breast cancer progression and suggest a rational window for intervention. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-05-01.