17. Terminal Duct Lobular Unit Involution of the Normal Breast: Implications for Breast Cancer Etiology

Figueroa, J., et al., 2014.

The human breast constantly is changing, from puberty to child-bearing to menopause to post-menopausal years. How well our bodies accomplish these changes, and how often and how completely, sometimes lead to changes that increase the risk of breast cancer.

One of these changes 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. “Terminal duct lobular units” (also called lobules) are the epithelial structures within the breast that produce milk during lactation. These also are a primary source of most breast cancer.

Scientists already know that greater degrees of involution in the breast (more often, more completely) have been linked to lower breast cancer risk, but they are unsure why. In this study, researchers wanted to see what happens to the TDLU (lobules) during the removal of milk production ability that triggers breast cancer in some people.


Using 1,938 samples from the Komen Tissue Bank, researchers looked at how involution occurs and progresses in the normal breast. Previously, researchers had only tissue samples from women having breast surgery, either for reduction or breast cancer, to study involution.

They developed three ways to assess involution in the normal tissue, using the KTB’s donor demographics such as age, pregnancies, breast feeding, menopause and overall health. Then they observed the state of involution in the samples according to that donor’s info. They developed models and charts to show and compare TDLU status according to such specific factors as smoking or family history of breast cancer or child bearing.


Researchers showed that age, menopausal status and child-bearing are determinants of TDLU, and other factors may produce additional side effects. Levels of TDLU varied widely among samples, and we need to study in greater detail, using normal samples, to better understand how this function sometimes makes it easy for cancer develop. One area in particular to examine more closely is age since last birth, which currently is not a risk factor but is an element this study exposed as significant in the TDLU involution process.

Why this study is important:

Using normal tissue samples along with the rich demographic information KTB collects from each donor, scientists could look at this biological function of involution in samples from women who had no history of breast disease. They drilled down using their lab work and the demographics to finely pinpoint aspects of involution that need to be studied further to understand what triggers breast cancer.