Menopause reshapes breast tissue, possibly raising cancer risk – study

More than three million cells have been mapped, showing how breast tissue changes with age, with the biggest shifts seen during menopause.

The research, described as the most detailed map of its kind so far, shows that as women age, all types of cells in breast tissue become fewer, those cells divide less often, and the tissue itself changes.

Together, these shifts create what the researchers call a “micro-environment”, meaning a local tissue setting in which cancer cells may find it easier to take hold.

Breast cancer is the most common cancer in women, accounting for 15 per cent of all new cases.

Four out of five cases occur in women over 50, and as many as one in seven women will develop breast cancer in their lifetime.

The study was led by scientists at the Universities of Cambridge and British Columbia.

The team used advanced imaging techniques to analyse breast tissue from more than 500 women aged 15 to 86, including biopsies taken for non-cancer-related reasons.

Pulkit Gupta from the Cancer Research UK Cambridge Institute at the University of Cambridge, joint first author, said: “Even though breast cancer affects well over 2 million women worldwide, we understand very little about why and when it occurs. As cells divide and replicate, they accumulate mutations that can drive cancer, but why is it that the body can get rid of these mutated cells when we’re younger, but struggles later in life?”

By combining the images with data on hormone receptors, immune cells and tissue architecture, the team mapped how breast tissue changes over time in unprecedented detail.

The findings point to reasons why breast cancer risk rises with age and why tumours in younger women differ biologically.

Gupta added: “Our map revealed that as women age, their breast tissue goes through major changes, with the most dramatic changes occurring at menopause.

“There are changes, too, during their twenties, possibly linked to pregnancy and childbirth, but these are far less pronounced.”

The map showed that milk-producing structures known as lobules shrink or disappear, while ducts, the channels that carry milk, become relatively more common.

The supporting layer around the ducts becomes thicker, fat cells increase and blood vessels decrease.

Changes were also seen in the immune environment. Younger breast tissue contains more B cells and active T cells, immune cells that help identify and kill cancer cells.

As tissue ages, these decline and are replaced by other immune cells linked to a more inflammatory and potentially less protective environment.

Co-senior author Dr Raza Ali from the Cancer Research UK Cambridge Institute at the University of Cambridge said: “We don’t know for certain why the types of immune cell change.

We can speculate that one reason may be because breast milk contains a high concentration of immunoglobulins, probably to help build the infant’s immunity, and these are produced by B cells.

At the same time, cells begin to interact with each other less. Immune cells and stromal cells, which form a supportive scaffold within tissue, become physically more distant from epithelial cells, the specialised cells lining the mammary ducts and lobules that produce and transport milk.

This may make it easier for pre-cancerous cells to escape control.

Co-senior author professor Samuel Aparicio from BC Cancer, University of British Columbia, Canada, said: “We’ve previously seen that age-dependent changes in oestrogen activity occur strongly in milk secreting cells of the breast and now we can see the surprising extent of changes in all cell types, including the immune system, with age.

“We are now seeking to understand the relationship between changes in immune cells and surveillance of early mutations that can arise in milk secreting cells over time.”

Dr Ali added: “It isn’t surprising that we should see fewer epithelial cells, as these play a role in producing breast milk, something that becomes less important with age, but the sheer scale of changes across the breast surprised us.

“What is clear from our map is that all of these changes create an environment where cancer cells that emerge naturally find it easier with age take hold and spread.”