Identifying metastatic breast cancer patients that may benefit from PARP inhibitor treatment.

Impact

Metastatic (or stage IV) breast cancer (MBC), accounts for most breast cancer deaths, and there is an urgent need to develop more effective treatment strategies. Two PARP inhibitors, Olaparib (LYNPARZA®) and talazoparib (TALZENNA®), are currently being used to treat MBC in patients with inherited BRCA1 or BRCA2 mutations. A critical question is whether PARP inhibitors may also be effective in MBC that harbor somatic (non-inherited) BRCA mutations, as is the case for ovarian cancer. Liquid biopsies, which can analyze circulating cell-free DNA (cfDNA) in the blood can detect tumor DNA that has sloughed off tumors and entered the bloodstream. As part of her Conquer Cancer study, supported by BCRF, Dr. Vidula and her team will test the ability of liquid biopsies to detect tumor BRCA mutations in patients with MBC and determine how well these patients respond to PARP inhibitor treatment.

Progress Thus Far

In preliminary studies, Dr. Vidula and her team analyzed liquid biopsies from patients with MBC for tumor BRCA mutations. They found BRCA mutations in 13.5 percent of tumor samples, largely in the absence of inherited BRCA mutations. Based on these findings, she and her team activated a clinical trial (NCT03990896) at Massachusetts General Hospital. In the past year, the trial also began enrolling at the University of California, San Francisco, MD Anderson Cancer Center, and Emory University. 

What’s next

In the upcoming year, Dr. Vidula will continue to screen and enroll patients, expanding to three additional sites. As this is a unique population, many patients need to be screened to identify those who have tumor specific BRCA mutations. They will ultimately enroll 30 patients in this preliminary study.