New work on a cell atlas of normal breast tissue is opening the way to early prediction and possibly prevention of breast cancer. This highly anticipated topic in breast cancer research will be the focus of the second Plenary Lecture during the 2024 San Antonio Breast Cancer Symposium^®.

Walid Khaled, PhD, will present Cell Atlases as Roadmaps in Cancer Immunology on Friday, December 13, from 8:30 to 9 a.m. CT in Hall 1 at the Henry B. Gonzalez Convention Center. Dr. Khaled is professor of tumor initiation and the co-leader of the Human Breast Cell Atlas initiative at the University of Cambridge.

“The breast is made of multiple cell types, including epithelial, immune, and stromal cells,” he said. “We wanted to chart the different cell types in healthy individuals and map how they change with normal physiological events, such as aging and parity. In addition, we also wanted to map how these cells change in healthy individuals who are at higher risk of developing breast cancer, such as BRCA carriers.”

“Our atlas revealed that the breast is a highly dynamic tissue, with many cell types changing with age and parity,” he continued, “but it also revealed that the composition of different cell types is markedly different in BRCA carriers from an individual with average risk.”

Two potential clinical applications are already emerging.

One approach is to identify potentially unhealthy cells in the pre-cancer setting as a way to prevent tumor development altogether. Dr. Khaled envisions that the Human Breast Cell Atlas could help identify potential targets for therapeutic prevention in high-risk individuals and act as a reference for assessing the success of any of these treatments.

“Even with the high degree of variability in healthy individuals, average risk tissue is remarkably different from breast cancer and is quite easy to spot,” Dr. Khaled said. “Single-cell genomics has also been quite transformative in understanding the heterogeneity of tumors — how diverse tumor cell types are within a cancer — and how the cancer responds at the cellular level to treatment.”

Better understanding and predicting response to treatment suggests a second application — identifying tumor persister cells that survive treatment and may regrow later as recurring or metastatic disease.

“We could use that understanding to be smart about the type of interventions that you could give an individual in the clinic,” Dr. Khaled said. “So depending on the specific profile of tumor cells, you might be choosing combinations or sequences of drugs rather than just one. That kind of information would be quite useful.”

Single-cell analysis remains expensive in the clinical setting. That makes it difficult to access for under-resourced communities or providers. And promising early results still have to be validated in larger populations.

“Studying the healthy states from as many individuals as possible will lead us eventually to understand how tumors evolve and develop,” Dr. Khaled said. “We should be thinking about interventions to intercept tumors before they develop.

“That obviously will not apply to every individual, but maybe to individuals at high risk,” he added. “We could do that in a very smart, targeted way using the kind of information that we glean from these cell atlases. Now is the time to put more effort and resources into prevention and therapeutic interventions in these kinds of analyses.”