Understanding PARP Inhibition in BRCA-Mutated Breast Cancer - Episode 3
Joyce A. O’Shaughnessy, MD: For HER2-negative breast cancers, we really have a new subtype, a new subset, of breast cancers, and those are breast cancers that have a mutation in BRCA1 or BRCA2. That’s almost always because the woman herself has a mutation that she’s inherited in BRCA1 or BRCA2, and that gets passed on to the breast cancer that she’s at higher risk of developing. That’s incredibly important for us to know these days in metastatic breast cancer because we now have agents approved to target the BRCA1 and BRCA2 mutations in the breast cancer called PARP [poly ADP ribose polymerase] inhibitors. This truly is a new diagnostic area of breast cancer. We have a new type of breast cancer that we must know about, and we have to do germline testing — we have to do a blood test on our patients—to find out if they have a BRCA1 or BRCA2 mutation that they’ve inherited.
The NCCN [National Comprehensive Cancer Network] guidelines, which are the most important national diagnostic and treatment guidelines that we have in cancer, have recently said that all women with metastatic breast cancer that’s HER2-negative should undergo testing, a blood test, to look for BRCA1 or BRCA2 mutations that they may have inherited. The reason it’s in HER2-negative disease is that BRCA1- or BRCA2-related breast cancers are rarely HER2-positive, so that’s why the focus is on HER2-negative disease.
Our NCCN guidelines say that all women with HER2-negative metastatic breast cancer, even if they don’t have any family history of breast cancer or ovarian cancer, should undergo BRCA1 or BRCA2 testing. Importantly, sometimes oncologists will send their tumor tissue for genetic analysis looking for mutations in the breast cancer that could lead to a treatment opportunity or a clinical trial opportunity for women who have metastatic breast cancer. Sometimes, you’ll find in the tumor tissue itself a BRCA1 or BRCA2 mutation, and that should also lead the woman to have blood testing to look for an inherited mutation. That’s another way to get there for testing of the germline. The germline is the DNA that the woman has inherited from her mother and father.
Transcript Edited for Clarity