Mariam Mansour

 Introduction. Pregnancy-associated breast cancer (PABC) is defined as any breast cancer diagnosed during pregnancy or within one-year post-partum. After cervical cancer, PABC is the most common malignancy affecting women during pregnancy. Ten-percent of all breast cancers diagnosed before the age of 40 (average age 32-38 years) in the United States are estimated to be associated with a recent pregnancy. PABC has been recognized for its more aggressive tumors, higher staging and poorer prognosis.^{1, 2, 4} This presentation sought to investigate some of the potential factors contributing to the unique malignancy of PABC. Methods. Samples of malignant epithelial tissue from tumor-associated stroma of PABC and non-PABC were isolated by last capture micro-dissection in order to determine whether high levels of estrogen and progesterone during pregnancy altered genetic expression.³ Additionally, mouse models have been utilized to examine local effects of stromal factors during pregnancy & lactation. Mammary adipose stromal cells (ASCs) were isolated from the mammary glands of mice and examined via functional assays, gene expression analysis and molecular & cellular assays in order to determine whether involution of the breast has an effect of mammary tumorigenesis.⁶ Furthermore, pregnancy-associated plasma protein-A (PAPPA), a protease involved in mitotic regulation of breast cells, has been investigated for it’s involvement in the development of cancer. PAPPA levels were manipulated in tissue samples of invasive breast cancers to determine whether it is involved in tumorigenesis.⁵ Results. Many estrogen & progesterone-regulated genes had expression patterns that correlated with the alteration in cell proliferation, metabolism and aggressiveness associated with PABC. Upregulated genes in the epithelia include genes involved in mitosis, the cell cycle, and nuclear division, while downregulated genes include tumor suppressor genes, and a large number of ribosomal genes.³ Locally, adipose stromal cells present during lactation (ASC-Ls) were found to be involved in the promotion and growth of breast cancer cells. They have a higher level of cellular retinoic acid binding protein-1 (crabp1), which alters their ability to retain lipids. This is also a feature of cancer-associated fibroblasts (CAFs). Inhibition of crabp1, eliminates tumor-promotion in the stromal environment.⁶ On the cellular level, PAPPA epigenetic silencing was observed in the cells of invasive breast tumors. Due to PAPPA’s critical function of modulating cell signaling pathways during normal cell division, knockout of this gene increases the invasiveness of breast tumors.⁵ Conclusions. PABC is a multi-faceted disease with many systemic, local and cellular factors associated with its pathogenesis. These alterations in the breast tissue during pregnancy may contribute to the more aggressive histological profile of PABC.

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