Age-related lobular involution as a target for breast cancer prevention

Our laboratory is defining features found in benign breast tissue after a breast biopsy that may be used to predict the individual risk of developing breast cancer.

One of the most informative features in this tissue is age-related lobular involution. Lobular involution is a natural process in which the milk-producing structures of the breast gradually regress with aging. Our research includes a cohort of more than 20,000 participants with benign breast disease diagnosed at Mayo Clinic. Those who completed the process of lobular involution had a substantially lower risk of breast cancer. However, about 40% of women do not complete lobular involution after menopause, which puts them at a markedly higher risk of breast cancer.

Our team is investigating why lobular involution stalls in some people. Our findings point to two Our team is investigating why lobular involution stalls in some people. Our findings point to two possibilities. One is cellular senescence, in which cells stop dividing but linger and promote inflammation. The other is changes in the breast's immune environment. Together, these two factors keep the tissue in a higher risk state rather than allowing it to settle into a protective, involuted state.

To test these ideas, we're using a living biobank of healthy breast tissue and organoids, including samples from women in the menopausal transition. These models can help us determine whether the stalled tissue can be shifted toward involution with treatment such as drugs that clear senescent cells or by adjusting the immune environment. Our goal is to develop a physiologically grounded approach to breast cancer prevention for people at greatest risk.