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Gene signature predicted spread of brain metastases in HER-2–positive patients
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CHICAGO — A 13-gene signature predicted rapid development of brain metastases in patients with HER-positive advanced breast cancer who have ER-negative tumors.
Recognizing the particularly high risk of brain metastases in HER-2–positive advanced breast cancer patients, Renata Duchnowska, MD, PhD, of the Military Institute of Medicine in Warsaw, Poland, and colleagues had previously developed a 13-gene signature strongly predicting for rapid development of brain metastases in this demographic.
In validating this gene signature, researchers analyzed 87 samples (discovery group) using cDNA synthesis, annealing, selection, extension, ligation and array hybridization — an independent validation group included 75 samples analyzed using quantitative reverse-transcriptase polymerase chain reaction. In addition, a 3-D culture validation model system evaluated immortal, non-tumorigenic human MCF10A breast epithelial cells with and without ectopic expression of HER-2 and RAD51, one of three genes of this group that is overexpressed in 13-gene signature.
According to the study results, median brain metastasis-free survival in the discovery group was 36 months for the “high” expression signature tumors vs. 66 months for the “low” expression tumors (P=.0068); brain metastasis-free survival in the validation group was 54 months for high expression vs. 86 months for low expression (P=.032).
Researchers observed that short brain metastasis-free survival was also associated with ER negativity. Brain metastasis-free survival in the cohort of high 13-gene signature and ER tumors was 31 months in the discovery group and 41 months in the validation group (P<.0001). In the other three groups, brain metastasis-free survival was observed to be 66 months in the discovery group vs. 77 months in the validation group (P=.02).
“Our study confirmed that 13-gene signature and ER negativity predict for rapid development of brain metastases in HER-2–positive advanced breast cancer patients,” Duchnowska said at a press conference. “We have also demonstrated that the RAD51 gene may promote aggressiveness in breast epithelial cells, and believe that this data, if confirmed for future studies, may be useful in the design of brain metastases preventive trials and may prompt new treatment strategies.”
For more information:
Duchnowska R. #505. Presented at: the 2012 American Society of Clinical Oncology Annual Meeting; June 1-5, 2012; Chicago.
Disclosure: Dr. Duchnowska reports no relevant financial disclosures.