The risk of breast cancer increases dramatically for women over the age of 50, but why has remained a mystery. However, researchers have uncovered a cellular basis for age-related breast cancer vulnerability.
Over 75% of women in the United States diagnosed with invasive breast cancers are over 50, and while age-related physiological changes – including endocrine profiles and alterations in microenvironments surrounding breast cancer cells – have been associated with increased cancer risks, the underlying cellular mechanisms remained unexplained.
Researchers from the Berkeley Laboratory determined that aging causes an increase in multipotent progenitors – a type of adult stem cell believed to be at the root of many breast cancers – and a decrease in myoepithelial cells that line milk-producing luminal cells which are believed to serve as tumour suppressors.
“This is a big step towards understanding the cellular basis for age-related vulnerability to breast cancer,” said LaBarge. “Now that we have defined some of the cell and molecular changes that occur in the epithelium during the aging process and we have the ability to assay them functionally, it should be possible to look for ways to avoid those states and perhaps even reverse them.”
Researchers generated a large collection of normal human mammary epithelial cells (HMECs) from mastectomies and cosmetic reduction surgeries derived from primary tissue in women aged 16 to 91 years for the study, published in Cancer Research.
“We do not know of another resource in the world like this for studying any type of human tissue,” said Mark LaBarge, study leader. “With this resource, we were able to perform functional studies of normal HMECs to observe the cellular changes that occurred with aging.”
The research also found that in finite-lifespan cultured and uncultured epithelial cells, the advancing years usher in a reduction of myoepithelial cells and an increase in luminal cells that express the proteins keratin and integrin α6. In women under 30, these are expressed almost exclusively in myoepithelial cells.
“The aging process therefore results in both a shift in the balance of luminal/myoepithelial lineages and to changes in the functional spectrum of multipotent progenitors that together appear to increase the potential for malignant transformation,” LaBarge said. “We corroborated our culture data with parallel analyses of in vivo samples, but we still have dots to connect to demonstrate that the changes relate to an increased risk of malignancy. All the signs are there though.”