Somatic Copy Number Alterations Are Prognostic in Metastatic Triple-Negative Breast Cancer

Submitted by onc_editor on Fri, 01/05/2018 - 14:54

A large genomic characterization study found specific somatic copy number alterations to have prognostic implications for metastasis, resistance, and novel therapeutic approaches in metastatic triple-negative breast cancer, published in the Journal of Clinical Oncology (online January 3, 2018; doi:10.1200/JCO.2017.76.0033).

Cell-free DNA may offer minimally invasive genome-wide profiling of tumor alterations without tumor biopsy, which may aid in patient prognosis. Triple-negative breast cancer is characterized by extensive somatic copy number alterations. However, further research is needed regarding somatic copy number alterations and their prognostic implications in this disease.

Daniel G Glover, MD, Ohio State University Comprehensive Cancer Center, and colleagues conducted a study to evaluate somatic copy number alterations in metastatic triple-negative breast cancer through cell-free DNA and to determine whether such DNA tumor fraction is associated with overall survival (OS) in metastatic disease. The retrospective cohort study enrolled 164 patients with biopsy-proved metastatic triple-negative breast cancer who received prior chemotherapy. Researchers performed low-coverage genome-wide sequencing of cell-free DNA from plasma.

Researchers reported tumor fractions of cell-free DNA for 96.3% of patients and somatic copy number alterations for 63.9% of patients. Additionally, they found that copy number profiles and the percentage of genome altered were significantly comparable between metastatic and primary triple-negative breast cancers.

Specific somatic copy number alterations were found to be more frequent in metastatic disease relative to paired primary tumors and primary triple-negative breast cancer in a few data sets – including The Cancer Genome Atlas and METABRIC.

Importantly, researchers reported that pre-specified cell-free DNA tumor fraction threshold of at least 10% was associated with worse metastatic survival (median, 6.4 vs 15.9 months) and remained significant, independent of clinicopathologic factors (HR, 2.14; 95% CI, 1.4-3.8; P < .001).

Dr Glover and colleagues concluded that “Specific somatic copy number alterations are enriched and prognostic in metastatic triple-negative breast cancer, with implications for metastasis, resistance, and novel therapeutic approaches.”—Zachary Bessette