Pubertal mammary gland development is a key determinant of adult mammographic density

Amita G. Ghadge, Pallave Dasari, Jennifer Stone, Erik W. Thompson, Rebecca L. Robker, Wendy V. Ingman

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


Mammographic density refers to the radiological appearance of fibroglandular and adipose tissue on a mammogram of the breast. Women with relatively high mammographic density for their age and body mass index are at significantly higher risk for breast cancer. The association between mammographic density and breast cancer risk is well-established, however the molecular and cellular events that lead to the development of high mammographic density are yet to be elucidated. Puberty is a critical time for breast development, where endocrine and paracrine signalling drive development of the mammary gland epithelium, stroma, and adipose tissue. As the relative abundance of these cell types determines the radiological appearance of the adult breast, puberty should be considered as a key developmental stage in the establishment of mammographic density. Epidemiological studies have pointed to the significance of pubertal adipose tissue deposition, as well as timing of menarche and thelarche, on adult mammographic density and breast cancer risk. Activation of hypothalamic-pituitary axes during puberty combined with genetic and epigenetic molecular determinants, together with stromal fibroblasts, extracellular matrix, and immune signalling factors in the mammary gland, act in concert to drive breast development and the relative abundance of different cell types in the adult breast. Here, we discuss the key cellular and molecular mechanisms through which pubertal mammary gland development may affect adult mammographic density and cancer risk.

Original languageEnglish
Pages (from-to)143-158
Number of pages16
JournalSeminars in Cell and Developmental Biology
Early online date11 Dec 2020
Publication statusPublished - Jun 2021


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