Triple negative breast cancers (TNBC, estrogen receptor negative, progesterone receptor negative, and human epidermal growth factor receptor 2 unamplified) represent a particularly aggressive form of breast cancer.
Although they represent about 10-20% of newly diagnosed invasive breast cancers, patients with TNBC often suffer worse outcomes compared to those with other subsets.
There are many reasons for this observation, among which are the apparent heterogeneity of TNBC’s, lack of a specific target which can be utilized therapeutically, and, in particular, development of chemoresistance.The breast medical oncology group at the University of Chicago Medicine is investigating ways in which we can improve outcomes of these patients with TNBC.
One of these projects is led by Suzanne Conzen, MD, professor of medicine, in collaboration with the clinicians and researchers in breast medical oncology.
Her research centers on the stress hormone (glucocorticoid) receptor (GR), its relationship to the biology of TNBCs, and its role in chemoresistance.
Conzen’s group and others have identified several GR-regulated target genes whose protein products mediate cell survival. Furthermore, tumor cell apoptosis induced by paclitaxel is inhibited by pretreatment with systemic glucocorticoids in xenograft models.
Gene expression data corroborated this finding and showed that there was a correlation between a tumor’s glucocorticoid receptor expression and early relapse in ER- breast cancers.
Thus, the hypothesis is that antagonizing ER- breast cancer’s glucocorticoid receptor activity will increase sensitivity to chemotherapy-induced cell death.
Our breast medical oncology group has completed an investigator-initiated randomized phase 1 clinical trial in which the standard chemotherapy nab-paclitaxel was combined with mifepristone, a GR antagonist provided by Corcept Therapeutics and already FDA-approved and available for commercial use in other indications.
Further studies are planned using combination chemotherapy gemcitabine + carboplatin with mifepristone.
This is an exciting area of active investigation led by clinician-scientists. We hope that this research and novel approach to treatment will translate to more effective therapies and ultimately better outcomes for these patients with TNBC.
Grace K. Suh, MD, is a medical oncologist who is dedicated to caring for patients with complex malignancies. Her mission is to provide cancer patients with evidence-based and state-of-the-art treatments while offering compassion and empathy to each patient and his/her family.