Since the late 1970s, clinicians have distinguished breast cancers types according to the presence or absence of certain receptors that sit on the surface of these tumor cells. Depending on the receptors found—namely, the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)—a doctor can get a better sense of the prognosis and which treatments might work.
Now, a study published this week in the Journal of Clinical Investigation proposes a new conceptual framework that classifies breast cancers based on whether the cells possess receptors for other molecules, such as androgen and vitamin D. Under this system, current cancer subtypes would be stratified into one of four groups.
“I’m very excited about this paper,” says Jorge Reis-Filho, a pathologist at the Memorial Sloan Kettering Cancer Center in New York who was not involved in the research. He adds that the proposed classification system could point to new therapies for breast cancers previously categorized as unlikely to respond to treatment.
In the new study, researchers sought to explain some of the diversity observed in human breast tumors by obtaining a more detailed understanding of normal breast cell subtypes. “I approached this question like an evolutionary biologist trying to figure out the ancestry of a species,” says study co-author Tan Ince, a pathologist at the University of Miami Miller School of Medicine.
Ince and his team scanned samples of normal breast tissue for proteins expressed in a “bimodal” or on/off pattern—highly expressed in some cells but completely absent in others. The researchers focused in on the handful of proteins that displayed this pattern. They subsequently characterized 11 previously undescribed subtypes of luminal cells—one of the two major epithelial cell types found in mammary glands—that each expressed distinct combinations of these proteins.