Lobular Involution: the Physiological Prevention of Breast Cancer

It truly is a remarkable event when traditional pathologic observations lead to new ideas about the prevention of cancer. In this issue of the Journal , Milanese et al. ( 1 ) , through a histologic review of breast biopsy specimens, show that the extent of age-related lobular involution is strongly associated with a reduced risk of breast cancer. Breast cancer risk decreased with increasing extent of involution in both high-risk and low-risk subgroups defined by age, epithelial atypia, reproductive history, and family history of breast cancer. Beginning in the premenopausal period, lobular involution is a physiologic process that occurs over many years whereby the parenchymal elements in the breast progressively atrophy and disappear ( 2 , 3 ) . The study reported by Milanese et al. represents a unique application of the Mayo Benign Breast Disease Cohort to investigate prospectively involution as a risk factor for breast cancer. It is the first study, to our knowledge, to substantiate a hypothesis that is based on pathologic and epidemiologic considerations that delayed involution is a major risk factor for breast cancer ( 4 , 5 ) .