Healthcare (Commonwealth Union) – Researchers have indicated that they have formed the most comprehensive map so far—built from more than three million cells—illustrating how breast tissue evolves as women grow older, including significant shifts during menopause.
The map shows that with age, the number of cells in breast tissue declines, their rate of growth slows, and the overall structure of the tissue changes. These alterations create a “microenvironment” that may allow cancer cells to grow more easily.
The findings, from a study led by scientists at the Universities of Cambridge and British Columbia, have been published in Nature Aging.
Breast cancer remains the most common cancer among women, accounting for around 15% of all newly diagnosed cases. About four in five cases occur in women over the age of 50, and roughly one in seven women will develop the disease during their lifetime.
Pulkit Gupta of the Cancer Research UK Cambridge Institute at the University of Cambridge, a joint first author of the study, indicated although breast cancer affects more than two million women globally, we still have limited understanding of how and when it develops. As cells divide, they pick up mutations that can lead to cancer—but it remains unclear why the body is better at clearing these abnormal cells when we are younger, and less effective as we age.
The researchers applied advanced imaging methods to examine breast tissue samples from over 500 women between the ages of 15 and 86. These samples included biopsies collected for non-cancer-related purposes.
By integrating the imaging data with information on hormone receptors, immune cell presence, and the structural organisation of the tissue, the team produced an exceptionally detailed map of how breast tissue evolves over time. Their results shed light on why the risk of breast cancer rises with age and why tumours in younger women have distinct biological characteristics.
Gupta indicated that their analysis showed that breast tissue undergoes significant transformation as women grow older, with the most pronounced changes occurring during menopause. Some alterations are also seen in women in their twenties—likely linked to pregnancy and childbirth—but these are much less substantial.
The map showed a clear decline across all cell types, both in their numbers and how frequently they divide. Structures responsible for producing milk, called lobules, either shrink significantly or disappear altogether. In contrast, the ducts that transport milk become more prominent, with their surrounding support layers thickening. There is also a rise in fat cells, while blood vessels become less abundant.
At the same time, the immune landscape shifts. In younger breast tissue, higher levels of B cells and active T cells help detect and eliminate potential cancer cells. As the tissue ages, these protective cells decrease and are replaced by other immune cells linked to a more inflammatory—and possibly less effective—environment.
Co-senior author Dr Raza Ali from the Cancer Research UK Cambridge Institute at the University of Cambridge noted that the reasons behind these immune changes are not fully understood. One possible explanation is that breast milk is rich in immunoglobulins, which support an infant’s immune system, and these are produced by B cells.
In addition, communication between cells weakens over time. Immune and stromal cells—which form the structural framework of tissue—become more physically distant from epithelial cells that line the ducts and lobules and are involved in milk production and transport. This growing separation may allow pre-cancerous cells to evade normal regulatory controls more easily.
Dr Ali says “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.”
