Not enough women are receiving genetic testing for BReast CAncer (BRCA) genes, despite unequivocal recommendations for universal testing in breast and ovarian cancer. A study published earlier this year in JAMA Open Network showed that germline BRCA testing continues to be underutilized, even for people with commercial insurance that covers the test.
BRCA mutations increase cancer risk
BRCA1 and BRCA2 genes are involved in repairing damaged DNA. When mutations arise in these tumor suppressor genes, cancer can develop. Testing for BRCA variants is useful particularly in breast and ovarian cancer, as well as other cancers such as prostrate and pancreatic cancer.
The lifetime risk of breast and ovarian cancer is significantly higher in women who inherit a BRCA mutation. The lifetime risk is 13 percent for breast cancer and 1.2 percent for ovarian cancer in the general female population. In contrast, in women who have inherited BRCA variants, the risk climbs to 44–72 percent and 11–44 percent for breast and ovarian cancer, respectively, depending on what mutation they carry and a host of other factors.
Current efforts to better understand genetic risks of cancer are ongoing. For example, Matthew J. Ferber, PhD, director of the Clinical Genome Sequencing Laboratory at the Mayo Clinic, revealed that, in partnership with the DNA sequencing laboratory, Helix, his group is conducting a study called Tapestry. As part of this study, they are examining the DNA of 100,000 Mayo Clinic patients to find germline changes in genes for hereditary ovarian and breast cancer, a form of hereditary colorectal cancer called Lynch syndrome, and familial hypercholesterolemia.
Genetic testing is currently recommended for anyone who has a high likelihood of carrying harmful BRCA1 and BRCA2 variants, as determined by risk assessment based on family history or prior cancer diagnosis. For those who have inherited BRCA mutations but do not yet present with cancers, cancer risk could be mitigated with enhanced screening, risk-reducing (prophylactic) surgery such as mastectomy or oophororectomy, and chemoprevention.
Universal genetic testing recommended following breast and ovarian cancer diagnosis
The evidence and best practices unequivocally support the need for universal testing for BRCA1 and BRCA2 variants in those who have been diagnosed with breast and ovarian cancers, including recommendations from the United States Preventive Services Task Force, National Comprehensive Cancer Network, and American Society of Clinical Oncology.
Confirming germline BRCA mutations in patients who have already been diagnosed is not only a preventive measure for their family members but also offers important clues for treatment. For breast cancer patients with BRCA mutations, the American Society of Clinical Oncology recommends certain drugs and procedures over others that would be effective in the general population not carrying BRCA mutations. These recommendations include use of poly-ADP-ribose polymerase (PARP) inhibitors, platinum agents, and bilateral mastectomy rather than breast-conserving therapy due to the significant risk of breast cancer in the other (contralateral) breast. In fact, adjuvant olaparib (brand name Lynparza) was recently approved by the U.S. Food and Drug Administration, to specifically target BRCA mutations in early breast cancer. For women with ovarian cancer who have BRCA variants, PARP inhibitors are similarly recommended over other types of drugs.
Lack of testing despite insurance coverage
Despite recommendations emphasizing the importance of BRCA genetic testing for prevention and therapy, the recent JAMA Open Network study by Chan et al. showed that there continue to be dismal rates of testing. The researchers from Harvard Medical School and their collaborators examined data from 2008–2018 from a large national commercial insurer to determine BRCA testing rates in women with ovarian cancer. From among 3,606 women with ovarian cancer, less than 40 percent of patients received germline BRCA testing.
Why is BRCA testing currently so underused? Genetic testing can be expensive, with the reimbursement rate for Medicare and Medicaid patients being about $200–$300 for single-gene Sanger sequencing and $2,000–$3,500 for next-generation sequencing (NGS). According to Ferber at the Mayo Clinic, NGS is becoming the “gold standard” because it is more sensitive, which is important for diagnosing individuals more accurately as well as generating more comprehensive genetic datasets for future research studies.
Ferber, who was not involved in the study by Chan et al., warns that significant underdiagnosis means that “we miss an opportunity to prevent disease,” thus affecting health outcomes and leading to a higher economic cost for the medical system in the long term. In accordance with current guidelines, he believes that “more testing is advantageous and justified, rather than a waste of resources.”
Furthermore, in the JAMA Open Network study, the insurance provider covered BRCA genetic testing for women diagnosed with ovarian cancer, so cost alone cannot explain the underutilization of genetic testing. Of note, the researchers observed that different medical specialties and health care facilities have different rates of testing, with oncologists and academic and cancer centers testing at higher rates than other physicians and community centers. Since a physician recommendation is a prerequisite for BRCA testing, this data highlights the need for interventions that target clinicians to help improve rates of genetic testing.
Along with increased public awareness and stringent clinical guidelines for cancer genetic testing, interventions for early detection can improve cancer therapy and even prevent the disease from occurring altogether.