Aggressive Form of Breast Cancer Linked to Gene Mutation

A new study from Tufts University School of Medicine finds why individuals who inherit a particular family of mutations have a higher risk of developing a very aggressive form of breast cancer.

Mutations in the BRCA1 tumor suppressor gene are linked to the development of a "basal-like" subtype of aggressive breast cancer which generally holds a very poor prognosis. Researchers wanted to look at whether BRCA1's role in regulating cell differentiation was associated with the increased development of basal-like breast cancer.

Lead study author Dr. Charlotte Kuperwasser, associate professor in anatomy and cellular biology at Tufts University School of Medicine, and a team of researchers mimicked the environment of intact human breast tissue in mice and looked at the kinds of tumors that formed when cells were exposed to cancer-promoting signals. They looked at this response in disease-free tissue with normal and mutant BRCA1 genes. The cells with normal BRCA1 grew into different kinds of breast cancer while the cells from women with BRCA1 mutations generally formed the aggressive basal-like tumors.

Researchers found the mutant cells were more apt to remain immature and contain elevated levels of a protein called Slug, which, when present in the breast, makes cells unable to undergo proper maturation. This delayed development is retained in basal-like breast cancers.

Breast cancer, aside from non-melanoma skin cancer, ranks as the leading cancer in U.S. women with the chance of developing invasive breast cancer at some point a little less than 1 in 8, or 12 percent, according to the Centers for Disease Control and Prevention (CDC).

The study appears in the journal, Stem Cell.