Genetic Biomarker as Potential Predictor of Platinum Sensitivity in Triple-Negative Breast Cancer
Posted: Friday, June 1, 2018
Researchers have identified two neighboring genes that may promote DNA damage and increased sensitivity to platinum-based therapy in triple-negative breast and serous ovarian cancers when overexpressed. The genes, Bloom helicase (BLM) and Fanconi anemia complementation group I (FANCI), have significantly increased DNA copy number and gene expression in cisplatin-sensitive cases. The study, led by Nicolai J. Birkbak, PhD, of the Technical University of Denmark in Lyngby, was published in the Annals of Oncology.
“A biomarker based on the expression levels of the BLM and FANCI genes is a potential predictor of platinum sensitivity in triple-negative breast cancer and ovarian cancer,” noted Dr. Birkbak and colleagues.
The investigators utilized previously published clinical and molecular data from two independent cisplatin-treated triple-negative breast cancer cohorts to conduct two differential analyses of gene expression and DNA copy number in cisplatin-sensitive versus cisplatin-resistant triple-negative breast cancer. BLM and FANCI were the only genes identified in both analyses for association in both cisplatin triple-negative breast cancer cohorts. In cisplatin-sensitive tumors, the copy numbers and mRNA expression of BLM and FANCI were both significantly higher.
The expression level of BRCA1 was also found to be significantly associated with cisplatin resistance in both cohorts (cohort 1, P = .0230; cohort 2, P = .0023), and BRCA1 expression levels were inversely correlated to those of BLM and FANCI. Response to paclitaxel was not significantly associated with BLM and FANCI, suggesting the correlation may prove to be specific to drug class.