19. Circulating Sex Hormones and the Terminal Duct Lobular Unit Involution of the Normal Breast

Khodr, Z., et al., 2014

One of the primary sources of breast cancer is “terminal duct lobular unit involution.” Involution is when mammary glands remove the milk-producing epithelial cells when they become redundant at weaning, resetting the glandular system, in a way. Involution also occurs throughout life as puberty, child-bearing and menopause change breast tissue structure.

But sometimes, involution may not occur frequently, or it may not be complete. Scientists know that lesser degrees of TDLU involution have been associated with increased risk of breast cancer, but they don’t have a full understanding of what factors influence involution.

In this study, they looked at sex hormones’ role in the involution process. Circulating hormones, such as progesterone, estradiol, testosterone and others, also are implicated in breast cancer risk. Could they also affect the involution process?


Researchers used 923 samples and data from Komen Tissue Bank donors to compare levels of hormones to involution status. They developed three ways of measuring estradiol, testosterone, sex hormone-binding globulin, progesterone and prolactin in the samples. Then they assessed the TDLU counts.


Among premenopausal women, the team found higher proactin levels were associated with higher TDLU counts (less involution) but higher progesterone levels were associated with lower TDUL counts (more involution). Among postmenopausal women, higher levels of estradiol and testosterone were associate with higher TDLU counts.

Why this study is important:

Both TDLU involution and circulating hormones present breast cancer risk factors. This study aimed to look at the connection between the two. The data suggest that select hormones are associated with TDLU counts and may influence breast cancer risk by delaying TLDU involution. This and future studies of the connections between hormones and TDLU involution may lead to new insights to how breast cancer forms.