Genetic Signature Identifies Patients with Aggressive Triple-Negative Cancers

A genetic test has the potential to help physicians identify patients with the most lethal forms of triple-negative breast cancer, a disease that requires aggressive and innovative treatment.

The test was able to distinguish between patients with a good or poor prognosis, even within groups of patients already stratified by existing tests, as well as to extend its predictions to patients with more advanced or difficult-to-treat cancers.

A team of international scientists led by those at the University of Chicago (IL, USA) mapped out a series of testable genetic signals, involving about 30 genes, and correlated the combination of signals with long-term outcomes in approximately 1,600 breast cancer patients. They studied genetic pathways around a gene known as Raf Kinase Inhibitory Protein (RKIP) to generate prognostic gene signatures. This RKIP-based pathway suppresses metastasis, the spread of cancer to distant sites, leading them to the Basic Leucine Zipper Transcription Factor 1(BACH1) Pathway Metastasis Signature (BPMS). They found that variations in the BPMS could predict prognosis for a wide array of patients, especially those with advanced or triple-negative disease.

The test was particularly informative for patients with triple-negative disease, where it could estimate the odds of a cancer spreading to other sites. It was also able to further stratify previously screened patients, such as those in the poor prognosis subgroup analyzed by MammaPrint (Agendia Inc.; Irvine, CA, USA) and the high-recurrence subgroup analyzed by OncotypeDX (Redwood, CA, USA). The predictive ability of the BPMS suggests that the genes it focuses on play a significant role in the progression of advanced breast cancers. Triple-negative cancers represent 14% to 20% of all breast cancers. They often recur after treatment, spread to the brain and lung, and develop resistance to standard chemotherapies. They occur more often in younger women, African-American women, Hispanic/Latina women and women who have BReast CAncer, early onset 1 (BRCA1) mutations.

Marsha Rosner, PhD, a professor and lead author, said, “Our test adds information to the existing US Food and Drug Administration (FDA, Silver Springs, MD, USA) approved tests. The BPMS is a significant predictive variable even after adjustment for all available clinical and prognostic factors. Specifically BPMS can significantly differentiate between higher and lower risk patients with the highly aggressive basal subtype.” The study was published on December 11, 2103, in the journal PLOS ONE.

Related Links:
University of Chicago
Agendia Inc.
OncotypeDX