A Prognostic Gene Signature for Predicting Chemotherapy Sensitivity and Patient Survival in ER-negative Breast Cancer

SUMMARY

• ER-negative (ER-) breast cancers make up 20% of all breast cancer diagnosis. However, no gene signature exists for predicting drug sensitivity and prognosis. Therefore, the clinical standard remains treating patients with generic chemotherapy despite possible drug resistance.
• Glucocorticoid receptor (GR) regulates many genes that contribute to tumor viability, aggressiveness, and recurrence suggesting that a network of GR target genes would be a better indicator of GR activity in TNBC than GR expression alone. The inventors analyzed 462 potential GR-modulated genes to identify a new strategy to further stratify breast cancer patients and provide a personalized treatment regimen.
• The inventors developed a 14-gene signature that can be used to predict prognosis of ER- breast cancer patients, including all subtypes of triple negative breast cancer. The gene signature can also be used to predict patient response to combination therapy with GR inhibitors to improve adjuvant treatment outcomes.
• In a validation cohort of 199 ER- breast cancer patients, the inventors found that the gene signature could predict relapse-free survival (p=0.00753, HR=1.94).

FIGURE

ADVANTAGES

ADVANTAGES

• Specific to ER- and triple negative breast cancer
• Improves the design and efficacy of combination therapies

APPLICATIONS

• Oncology prognosis
• Precision medicine

PUBLICATIONS

• West, DC; et al. Discovery of a glucocorticoid receptor (GR) activity signature using selective GR antagonism in ER-negative breast cancer. Clin Cancer Res. 2018 Jul 15; 24(14): 3433-3446.