A pathology researcher at the University of Rochester Medical Center believes she’s discovered an important phenomenon in normal-looking breast tissue that could foreshadow an aggressive tumor known as triple-negative breast cancer.
Xi Wang, M.D., recently reported her findings in Human Pathology; she also presented the data at the U.S. and Canadian Academy of Pathology’s annual international meeting in 2016, the largest international meeting in the pathology field. Wang analyzes hundreds of breast tissue samples each month and based on her observations came up with the hypothesis that an alteration in the p53 gene might be the beginning of a cell’s cascade toward becoming fully cancerous.
P53 is a well-known tumor-suppressor gene. When it’s acting as it should, p53 keeps cancer at bay. But when it is mutated, it no longer suppresses cancer cells. It’s frequently mutated in lung cancer and also commonly mutated in a type of high-grade ovarian cancer. In breast cancer, the p53 mutation is detected in less than 25 percent of cases, Wang said, but the frequency is much higher in triple-negative breast cancer, which is much harder to treat.
Her latest research looked at normal/benign tissue samples from women who also carried the BRCA1 or BRCA2 genetic mutations, which increase the chances of getting breast cancer by more than 50 percent, and significant boosts the likelihood that breast cancer will be the triple-negative subtype. Results showed that p53 is more frequently altered in the seemingly “normal” breast tissue in BRCA carriers, compared with the general population. This may help to explain why BRCA carriers are at much higher risk for aggressive cancer.
These p53 mutated breast cells are not proliferating as crazy as tumor cells and have not yet developed into cancer, Wang said. “But they are funny looking and now I will look at them differently because they might be part of a signature for cancer.”
With so many diverse types of breast cancer, it’s important to be able to identify high-grade disease at the earliest point in time to inform treatment decisions.
Although the science is still in its early stages, Wang said, being able to recognize a p53 signature in normal breast cells could someday give high-risk women more information as they are deciding whether to remove their breasts. Currently, however, there is no standard way to screen for p53 mutations in breast tissue.