Spatial biology of the breast and variation in cancer risk

Breast cancer risk and the type of breast cancer people develop can differ across populations. These differences may be established in the breast tissue itself and in the signals that surround its cells long before a tumor develops.

Our lab is mapping these differences to understand more about the risk of breast cancer and how to reduce it.

To do this, we built a living biobank of healthy breast tissue donated by people from all backgrounds, spanning a wide range of ages and reproductive histories. For each donor, we preserve matched materials (fixed tissue that retains its architecture), along with organoids and living cells. This way, what we see in tissue can be tested directly in the laboratory.

We're studying this tissue using high-resolution imaging and spatial profiling. This process lets us measure which cells are present and how they're organized relative to one another. Using these tools, we have found that histologically healthy breast tissue is not the same in everyone.

Some differences track with ancestry and are concentrated in specific regions of the breast rather than spread evenly throughout it. For example, we found distinct patterns of growth-signaling and developmental pathways, including the Hedgehog and vitamin D pathways, that can tip cells toward a higher risk state.

Because we can test these tissues as living models, we can investigate whether such states are reversible. We use existing drugs to see whether the high-risk pattern can be turned back toward a healthy state.

Our goal is to assemble these findings into an atlas of the healthy breast and into simple, measurable markers that can be validated in large cohorts of participants. By grounding risk prediction in the biology of each person's tissue, we hope to make breast cancer prevention more accurate and more personalized.