The Benefits of Genetic and Genomic Testing
At our center, we employ multiple laboratory tests for genomic and genetic makeup that allow us to determine which specific medications and treatments may be most appropriate for each patient. We utilize both the Invitae Genetic Test and the Myriad myRisk® Hereditary Cancer testing. The Myriad test is a 35-gene panel that identifies elevated risk for eight hereditary cancers. There are a host of genetic pathways and mutations that a patient may have (including BRACA 2, BRCA1, HOXB13, ATM, CHEK2, and CDK1), and they can tell us whether or not a patient is likely to respond well to a particular agent. For example, we know that a patient with positive BRCA1 and especially positive BRCA2 gene mutations will most likely have a shorter effective run with the androgen-blocking drugs Xtandi® and Zytiga®.
Another lab test analyzing serum is called a “droplet digital PCR assay,” and it can also help us determine which patients will best respond to those chemical agents, Xtandi® and Zytiga®. It should be noted that genetic markers are also important in light of the patient’s family history. We want to know what the family history is with regard to other cancers. We can see that a patient’s daughters may be prone to breast cancer or ovarian cancer; and now even colon and pancreatic cancers enter the picture in the spectrum related to prostate cancer. These cancers are essentially on the same page in our genetic makeup. Melanoma is also now seen to be genetically related to prostate cancer, and all of these cancers may occur at increased frequency in the patient tested.
Both Xtandi® and Zytiga® have a side effect profile similar to that of hormonal therapy. With patients for whom Xtandi® and Zytiga® are not effective or are unlikely to be effective as indicated by positive genetic markers (BRCA1 and BRCA2), we may prescribe Lynparza® (olaparib), which is known as a PARP inhibitor (poly ADP-ribose polymerase). Many patients fare quite well with Lynparza®. Another immunotherapy agent, Keytruda® (pembrolizumab) is known as a PD1 inhibitor. We are finding that patients who are not responding well to Lynparza may benefit from Keytruda. We have a growing arsenal of medications at our disposal for patients with advanced or recurrent disease. Both hormonal therapies and immunotherapies are associated with far less toxicity than chemotherapy as they are “targeted therapies”
While genetic testing is important for the patient’s siblings and children, (and also for the patient on occasion), there is even greater importance in sampling the actual cancerous tissue removed from the patient in order to identify somatic mutations. This is known as comprehensive genomic profiling (CGP). This test can help identify exactly which treatment may benefit the patient (e.g. AR-7 mutations suggest resistance to Xtandi®/Zytiga® while HRR gene mutations predict response to Lynparza). Checkpoint inhibitors (e.g. PD-1) suggest sensitivity to pembrolizumab. We have been using FoundationOne ®CDx as the best genomic test currently available for identifying somatic mutations. This test searches 324 genes for cancer-relevant mutations in the DNA.
* For more information about the Myriad myRisk® Hereditary Cancer Test, click here: https://myriad.com/products-services/hereditary-cancers/myrisk-hereditary-cancer/
* To learn more about Invitae Genetic Testing, click here: https://www.invitae.com/en/detect-hereditary-prostate-cancer/?utm_source=DHPC&utm_medium=poster&utm_campaign=fall2019
* The National Comprehensive Cancer Network (NCCN) offers patients recommendations on genetic testing and describes Medicare coverage here: https://myriad.com/products-services/hereditary-cancers/myrisk-hereditary-cancer/
* Additional information on the FDA approved FoundationOne ®CDx Test is available here: https://www.foundationmedicine.com/test/foundationone-cdx