Effects of radiation therapy on breast epithelial cells in BRCA1/2 mutation carriers

Women carrying BRCA1and BRCA2mutations have significantly elevated risk of developing breast and ovarian cancers. BRCA1-associated breast cancer likely originates from progenitors of the luminal epithelial lineage. Recent studies indicate that radiation therapy (RT) for BRCA1cancer patients is associated with lower incidence of developing subsequent ipsilateral breast cancer. In the current study, we analyzed tumor-free breast tissue procured via prophylactic bilateral mastectomy from three BRCA1and one BRCA2mutation carriers, who had been previously treated with RT for unilateral breast cancers. Freshly isolated breast cells from the irradiated and nonirradiated breast tissue of the same individuals were subjected to flow cytometry, using established cell-surface markers. Two out of the three BRCA1carriers and one BRCA2carrier exhibited significantly diminished luminal cell population in the irradiated breast versus the nonirradiated side. There was also RT-associated reduction in the colony-forming ability of the breast epithelial cells. Our finding suggests that prior RT could result in the depletion of the luminal epithelial compartment and thus reduced incidence of BRCA1/2-associated breast cancer.