Gene Expression Pattern in Surrounding Normal Tissue Linked to Breast Cancer Prognosis
A gene expression pattern in the noncancerous tissues surrounding estrogen receptor-positive breast cancer is associated with lower 10-year survival rates. Approximately 70% of breast cancers are estrogen receptor-positive.1
“Most of the studies to date that have tried to develop predictive biomarkers for cancer progression have focused on tumor cells themselves,” said Melissa Troester, PhD, a Lineberger member and an associate professor in the Gillings School of Global Public Health Department of Epidemiology at the University of North Carolina at Chapel Hill, and first author of the study.
“This suggests that other factors in the microenvironment of the tumor may be important in predicting prognosis.”
Researchers assessed several genomic characteristics of the normal-appearing tissue surrounding tumors. The samples came from the Cancer Genome Atlas, a collaborative effort to map genomic and epigenomic changes that drive cancer.
Approximately 40% of the samples had a defect in DNA or RNA, although the presence of defects was not associated with differences in survival.
“Breast cancer researchers have recognized that likely, breast-conserving therapy is leaving behind tissue or cells that are either partially or fully transformed,” Troester explained.
“But these cells are targeted by therapy after surgery, keeping recurrence rates low for breast-conserving therapy.”
Radiation therapy after breast-conserving surgery has been shown to reduce recurrence rates. As this study found cells with genetic defects as much as 4 cm from the tumor, these results support other research indicating wider surgical margins achieve no benefit.
“This says it's not sufficient to just excise the tumor with the wider margin: those mutations are still present at even farther distances from the tumor. This tells us that radiotherapy and adjuvant chemotherapy are pretty effective in eliminating cells with those DNA defects,” Troester explained.
Analyses of gene expression patterns in normal tissue beyond the tumor margins revealed 2 different subtypes of tissue near the tumor. One of which is associated with significantly lower survival at 10 years.
“Gene expression subtypes of the surrounding tissue may reflect the composition and biological activity of the breast tissue in those patients,” Troester said.
“This suggests that it may be possible to add information from the tumor microenvironment to standard clinical information to predict prognosis for patients.”
1. Troester MA, Hoadley KA, D'Arcy M, et al. DNA defects, epigenetics, and gene expression in cancer-adjacent breast: a study from The Cancer Genome Atlas [published online May 4, 2016]. npj Breast Cancer. doi:10.1038/npjbcancer.2016.7