ORLANDO, Fla., Feb. 17, 2017 /PRNewswire/ — New research suggests that a substantial fraction of patients with prostate cancer and a positive family history are at high risk of an inherited genetic mutation that might help inform their treatment options. Among those men with prostate cancer meeting NCCN guidelines for testing, these initial data support the concept that particulars in the family history cannot be used to predict pathogenic variants.
The research was presented at the 2017 Genitourinary Cancer Symposium, February 16-18, in Orlando, Florida. Patients in the study, which was conducted by the Tulane Cancer Center in New Orleans, were tested using a commercially available panel of 25-79 cancer-related genes from Invitae (NYSE: NVTA), one of the fastest growing genetic information companies.
The study, Inherited pathologic mutations and family history in patients with prostate cancer (Abstract #185), was designed to find, evaluate, and characterize pathogenic mutations related to DNA repair defects in prostate cancer patients, using both detailed family history and germline genetic testing. The study screened 605 prostate cancer patients from Tulane Cancer Center for their detailed family histories. Of those, 147 patients reported a family history that met NCCN guidelines for genetic testing. Those 147 patients then underwent genetic testing using a commercially available panel from Invitae of 25-79 cancer-related genes for mutations and selected exonic deletions/duplications.
Approximately one in six of the patients tested (16.3%) were found to have a pathogenic variant in a cancer-related gene while 42.9% showed no significant germline mutations and 40.8% were found to have a germline variant of unknown significance (VUS). The results show a significant fraction of patients with family history exhibited pathogenic genetic changes, with the majority of mutations found in the DNA repair genes. Additionally, in prostate cancer, evidence continues to increase that genetic testing for mutations in DNA-repair genes such as BRCA1 and BRCA2 can impact the care of patients and the health of their families. For example, if a prostate cancer patient is found to carry a mutation in a DNA-repair gene, his close biological relatives may share that mutation and be at increased risk for prostate, breast, ovarian, and other cancers.
“Genetic information is increasingly impacting therapeutic decisions for prostate cancer patients and their family members. Genetic testing of family members can help identify those at risk earlier and enable physicians to provide more proactive care,” said Oliver Sartor, MD, Laborde Professor of Cancer Research at Tulane Cancer Center and one of the authors of the study. “The findings indicate a significant yield of mutations in patients with a family history. Given small family sizes and a frequent lack of information about relatives, we suspect that broader genetic testing of prostate cancer patients may be warranted, beyond what current guidelines recommend, as mutations may be found in patients without a known family history of cancer.”
The study presented at 2017 Genitourinary Cancers Symposium builds on earlier research published in 2016 in the New England Journal of Medicine demonstrating that inherited DNA-repair gene defects are more common than expected. In that study, mutations found in multiple DNA repair genes were significantly increased in metastatic prostate cancer patients. Importantly, the DNA-repair manuscripts in prostate cancer clearly show a family history of prostate cancer is not always relevant in determining risk. The NEJM study suggested that broader testing of patients with metastatic prostate cancer without regard to family history could increase the yield of actionable mutations identified. (N Engl J Med 2016;375:443-53)
“Our understanding of the role of genetic changes in influencing a man’s risk of developing prostate cancer has deepened, just as it has for a woman’s risk for breast and ovarian cancer. We also know genetic information can help predict which men are more likely to develop aggressive disease,” said Robert Nussbaum, MD, chief medical officer of Invitae. “A broad hereditary cancer panel can provide clinicians with information on clinically significant genes, helping identify men at greater risk for prostate cancer who should undergo more extensive surveillance, thereby allowing the cancer to be detected at earlier stages. Through cascade testing in families, finding the first such mutation in a man with prostate cancer can alert other relatives, men and women, of a substantially higher risk for breast, ovarian, prostate, and pancreatic cancer. Finally, there is the possibility of providing better personalized therapies for those with this potentially lethal disease by highlighting treatments that target tumors deficient in homologous recombination repair pathways.”
Comprehensive genetic testing for prostate cancer
Invitae has more experience with hereditary cancer testing in prostate cancer than most other laboratories due to its broad, comprehensive menu and flexible ordering approach. The Invitae Prostate Cancer Panel analyzes up to 14 genes that are associated with a hereditary predisposition to prostate cancer. In addition, Invitae’s offers its 42-gene Common Hereditary Cancers Panel and its 80-gene Multi-Cancer Panel for clinicians seeking a broader look at their patient’s genetic risk. Invitae provides results in as few as 10 calendar days (14 days on average).
Research published in the Journal of Clinical Oncology has shown BRCA1 and BRCA2 mutations are both known to increase the lifetime risk of prostate cancer by about 20%. HOXB13 mutations are associated with an up to 60% lifetime risk of prostate cancer, according to another study. In addition, African American men with prostate cancer may be more likely to have germline mutations in the BRCA1 and BRCA2 genes than Caucasian men with prostate cancer, as presented during the 111th Annual Scientific Meeting of the American Urological Association in 2016. According to the American Cancer Society, nearly three million men have been diagnosed with prostate cancer in the United States.
To help support clinicians and their patients, Invitae offers its clinicians access to its Clinical Consult Service, where Invitae’s expert team of medical geneticists and genetic counselors provide support through the entire testing process to select the right test, clarify results, and review individual patient cases at no additional charge. Invitae also makes genetic counseling services available as needed.
Invitae Corporation’s (NYSE: NVTA) mission is to bring comprehensive genetic information into mainstream medical practice to improve the quality of healthcare for billions of people. Invitae’s goal is to aggregate most of the world’s genetic tests into a single service with higher quality, faster turnaround time, and lower price than many single-gene and panel tests today. The company currently provides a diagnostic service comprising hundreds of genes for a variety of genetic disorders associated with oncology, cardiology, neurology, pediatrics, and other rare disease areas. Additionally, the company has created a Genome Network to connect patients, clinicians, advocacy organizations, researchers, and drug developers to accelerate the understanding, diagnosis, and treatment of hereditary disease. For more information, visit our website at www.invitae.com.