Chromatin Remodeling and Pregnancy-Induced Differentiation
Breast cancer is the most frequently diagnosed cancer in postmenopausal women and the leading cause of cancer death in females worldwide . The global incidence of breast cancer has gradually increased over the last few decades [1, 2]. Although the reasons of this increase are uncertain, it is known that the breast cancer risk is reduced in women who gave birth to a child before age 24  a reduction that is enhanced by breast-feeding and multiparity [4, 5]. Experimentally it has been demonstrated that the protection conferred by pregnancy is mediated by the differentiation of the breast, a physiological process driven by the complex hormonal milieu created by the placenta and the fetus [6–8]. The postulate that the degree of differentiation acquired through an early pregnancy changes the genomic signature that differentiates the lobular structures of early parous (P) women from those of nulliparous (NP) women has been demonstrated through the enriched analysis of the genomic profile of breasts of parous and nulliparous postmenopausal and premenopausal women [9, 10] and of rodent models [6–8, 11, 12]. These findings have allowed researchers to demonstrate that significant differences in the expression of genes controlling differentiation and transcription exist between groups that differ in their parity history. These data explain at molecular level the basis of the protective effect of pregnancy and establishes a functional genomic signature of breast cancer risk reduction, confirming a postulate published in 1997 .
KeywordsDepression Estrogen Lysine Luminal DAPI
We, the authors, acknowledge the contributions of the many members of the Breast Cancer Research Laboratory at the Fox Chase Cancer Center, especially Drs. Y Su, R. Lopez, and F. Sheriff, who have worked with us to generate the data described in Sect. 7.8 incorporated into this chapter and allowed us to elaborate it into a unified concept.
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