Pubertal mammary development as a "susceptibility window" for breast cancer disparity

Abstract

Factors such as socioeconomic status, age at menarche and childbearing patterns are components that have been shown to influence mammary gland development and establish breast cancer disparity. Pubertal mammary gland development is selected as the focus of this review, as it is identified as a "window of susceptibility" for breast cancer risk and disparity. Here we recognize non-Hispanic White, African American, and Asian American women as the focus of breast cancer disparity, in conjunction with diets associated with changes in breast cancer risk. Diets consisting of high fat, N-3 polyunsaturated fatty acids, N-6 polyunsaturated fatty acids, as well as obesity and the Western diet have shown to lead to changes in pubertal mammary gland development in mammalian models, therefore increasing the risk of breast cancer and breast cancer disparity. While limited intervention strategies are offered to adolescents to mitigate development changes and breast cancer risk, the prominent solution to closing the disparity among the selected population is to foster lifestyle changes that avoid the deleterious effects of unhealthy diets.

Keywords: Breast cancer disparity; Breast cancer risk; Health intervention; Pubertal mammary gland development.

Fig. 1

Overview of different stages of mammary gland development. Schematic representation of mammary gland development from a rudimentary structure at birth, through tightly regulated phases of growth such as puberty, associated with the formation of TEBs and increased proliferation, differentiation and elongation/branching of the ductal tree. After puberty the gland is fully formed and becomes quiescent, until pregnancy. Hormonal factors during pregnancy leads to increased proliferation, differentiation, side branching and alveologenesis to form a functioning gland for lactation. Following lactation is a stage of tightly controlled apoptosis during involution to return the gland to a quiescent state.

Fig. 2

Factors influencing pubertal mammary gland development. The tightly regulated window of pubertal mammary gland development has shown to be a key window of “cancer susceptibility” specific when looking at lifestyle factors, such as diet and obesity. Diets such as; a diet high in fat, N-6 PUFA, the Western diet and lifestyle factors such as obesity have been shown in various in vivo models to lead to dysregulation of development and increased hormonal and growth factor status as well as immune/stromal cell activity. Meanwhile other diets high in N-3 PUFA and phytoestrogens have been shown to have protective effects in cancer susceptibility when consumed during puberty.